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Fan Z, Hong R, Li S, Kong L, Zhou Q, Ma T, Chen H, Pan C. Embryonic exposure to GenX causes reproductive toxicity by disrupting the formation of the blood-testis barrier in mouse offspring. Toxicology 2025; 515:154161. [PMID: 40268268 DOI: 10.1016/j.tox.2025.154161] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2025] [Revised: 04/08/2025] [Accepted: 04/17/2025] [Indexed: 04/25/2025]
Abstract
As a replacement for perfluorooctanoic acid, hexafluoropropylene oxide dimer acid, commercially referred to as "GenX", has attracted significant attention. However, a comprehensive understanding of the reproductive systems of male offspring exposed to GenX is lacking. This study aimed to investigate how embryonic exposure to GenX affects the reproductive development of male offspring and the underlying mechanisms. We administered GenX daily via gavage (2 mg/kg body weight/day) to the mice from day 12.5 of pregnancy until delivery. Our results suggested that embryonic exposure to GenX led to delayed onset of puberty in male offspring, with destruction of the testicular structure, disruption of the blood-testis barrier, decreased serum testosterone levels, decreased sperm count, impaired sperm motility, and increased rates of sperm abnormalities. We investigated the mechanism of blood-testis barrier breakdown in vitro by treating Sertoli cells (TM4) with GenX. GenX exposure caused the accumulation of senescent TM4 cells, decreased their glutathione (GSH) levels, and increased their oxidized glutathione levels. GenX inhibited glutaminase activity in TM4 cells, leading to decreased GSH synthesis, increased intracellular oxidative stress, and subsequent TM4 cell senescence, ultimately compromising the blood-testis barrier. Our findings indicated that embryonic exposure to GenX may cause Sertoli cell senescence by altering glutamine metabolism, disrupting the blood-testis barrier, and resulting in abnormal reproductive development in male offspring.
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Affiliation(s)
- Zhencheng Fan
- Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, China; Department of Orthopedics, Affiliated Hospital of Yangzhou University, Yangzhou, China
| | - Runyang Hong
- Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, China; Key Lab of Non-Coding RNA Basic and Clinical Translational Research, Yangzhou University, Yangzhou, China
| | - Shuhao Li
- Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, China; Key Lab of Non-Coding RNA Basic and Clinical Translational Research, Yangzhou University, Yangzhou, China
| | - Liang Kong
- Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, China; Key Lab of Non-Coding RNA Basic and Clinical Translational Research, Yangzhou University, Yangzhou, China
| | - Qiyue Zhou
- Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, China; Key Lab of Non-Coding RNA Basic and Clinical Translational Research, Yangzhou University, Yangzhou, China
| | - Tan Ma
- Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, China; Key Lab of Non-Coding RNA Basic and Clinical Translational Research, Yangzhou University, Yangzhou, China
| | - Hao Chen
- Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, China; Department of Orthopedics, Affiliated Hospital of Yangzhou University, Yangzhou, China.
| | - Chun Pan
- Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, China; Department of Orthopedics, Affiliated Hospital of Yangzhou University, Yangzhou, China.
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Nunes ADC, Pitcher LE, Exner HA, Grassi DJ, Burns B, Sanchez MBH, Tetta C, Camussi G, Robbins PD. Attenuation of Cellular Senescence and Improvement of Osteogenic Differentiation Capacity of Human Liver Stem Cells Using Specific Senomorphic and Senolytic Agents. Stem Cell Rev Rep 2025:10.1007/s12015-025-10876-x. [PMID: 40220121 DOI: 10.1007/s12015-025-10876-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/02/2025] [Indexed: 04/14/2025]
Abstract
Expansion of adult stem cells in culture increases the percent of senescent cells, reduces their differentiation capacity and limits their clinical use. Here, we investigated whether treatment with certain senotherapeutic drugs would reduce the accumulation of senescent cells during expansion of human liver stem cells (HLSCs) while maintaining their differentiation capacity. Our results demonstrate that chronic treatment with the senomorphic XJB-5-131 or the senolytics cocktail D + Q reduced the number of senescent cells and significantly reduced the expression of senescence-associated genes and several inflammatory SASP factors in later passage HLSCs. Additionally, treatment with XJB-5-131 and D + Q improved the capacity of HLSCs to undergo osteogenic differentiation following extensive in vitro expansion. Overall, our data demonstrate that treatment with XJB-5-13 or D + Q results in a reduction in the percentage of replication-induced senescent HLSCs and likely other types of adult stem cells and improve the potential therapeutic use of later passage human stem cells.
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Affiliation(s)
- Allancer D C Nunes
- Masonic Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, Minnesota, USA
| | - Louise E Pitcher
- Masonic Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, Minnesota, USA
| | - Henry A Exner
- Masonic Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, Minnesota, USA
| | | | - Brittan Burns
- Masonic Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, Minnesota, USA
| | - Maria Beatriz Herrera Sanchez
- Molecular Biotechnology Centre, University of Torino, Torino, Italy
- 2i3T Societ Per la Gestione Dell'incubatore di Imprese e per il Trasferimento Tecnologico Scarl, University of Torino, Torino, Italy
| | | | - Giovanni Camussi
- Molecular Biotechnology Centre, University of Torino, Torino, Italy
- Department of Medical Sciences, University of Torino, Torino, Italy
| | - Paul D Robbins
- Masonic Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, Minnesota, USA.
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Luo Q, Liu L. Adipose-derived stem cells regulate mitochondrial dynamics to alleviate the aging of HFF-1 cells. In Vitro Cell Dev Biol Anim 2025; 61:357-367. [PMID: 39871034 DOI: 10.1007/s11626-025-01017-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Accepted: 01/04/2025] [Indexed: 01/29/2025]
Abstract
The objective of this study is to explore how adipose-derived stem cells (ASCs) regulate mitochondrial structure and function and the impact of this regulation on slowing cellular senescence. HFF-1 cells were induced by H2O2 to establish a cellular senescence model, and ASCs or Mdivi-1 (mitochondrial fission inhibitor) was added. MTT examined the cell proliferation; flow cytometry detected mitochondrial membrane potential as well as apoptosis and cell cycle; kit measured ATP production; ELISA analyzed the levels of interleukin-6 (IL-6), interleukin 1 beta (IL-1β), tumor necrosis factor alpha-like (TNF-α), glutathione (GSH), malondialdehyde (MDA), and superoxide dismutase (SOD); Western blotting and qRT-PCR detected the expression of protein and mRNA levels; and β-galactosidase staining observed the degree of cellular senescence. Compared to normal HFF-1 cells, senescent HFF-1 cells exhibited weaker proliferative capacity, marked apoptosis, and G0-G1 cell cycle arrest. These cells also showed lower mitochondrial membrane potential and ATP production, higher expression of inflammatory factors, oxidative damage, and increased levels of senescence. Treatment with Mdivi-1 or ASCs enhanced HFF-1 cell proliferation, reduced apoptosis and cell cycle arrest, increased mitochondrial membrane potential and ATP production, decreased the expression of inflammatory factors, and mitigated oxidative stress, thereby reducing the degree of cellular senescence. Concurrent intervention with Mdivi-1 and ASCs further diminishes the impacts of cellular senescence. In conclusion, ASCs regulate mitochondrial dynamics (promoting mitochondrial fusion and inhibiting mitochondrial fission), enhance ATP production, and upregulate mitochondrial membrane potential, thereby alleviating cell cycle arrest, apoptosis, inflammatory responses, and oxidative stress induced by senescence in HFF-1 cells.
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Affiliation(s)
- Qi Luo
- Department of Plastic Surgery, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, 421002, Hunan, China
| | - Ling Liu
- Department of Outpatient Service, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, 421002, Hunan, China.
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Woo J, Ji H, Jeon K, Kim H, Yoon S, Hwang Y, Cho E, Park D, Jung E. Anti-skin aging effects of Gosori liquor lees extract by regulating interactions between senescent fibroblasts and adipose-derived stem cells. Int J Cosmet Sci 2025. [PMID: 39838700 DOI: 10.1111/ics.13046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2024] [Revised: 12/13/2024] [Accepted: 12/23/2024] [Indexed: 01/23/2025]
Abstract
When cellular ageing is accelerated by various extrinsic/endogenous stimuli, regenerative function deteriorates, and enriched secretomes, such as the senescence-associated secretory phenotype (SASP), contribute to chronic inflammation and cause matrix degeneration. SASPs from senescent fibroblasts exacerbate cellular senescence via autocrine signalling and also accelerate skin ageing through the induction of neighbouring cell senescence via paracrine signalling. The interaction between dermis fibroblasts and their neighbours, adipose-derived stem cells (ADSCs) in the hypodermis, which lies deep in the dermis, is a potential target for skin ageing. In this study, we observed that an extract of the lees of Gosori liquor (GLE), a traditional Korean liquor made by fermenting millet and rice, suppressed the senescence of fibroblasts, including SASP production, in a replicative senescent model. We further examined whether the anti-ageing effects of GLE on fibroblasts affected the cellular senescence of their surrounding cells, ADSCs. The results showed that senescence factors in ADSCs were suppressed by culture medium from senescent fibroblasts (SF-CM) treated with GLE compared to the SF-CM-only treated group. Furthermore, the regenerative ability of ADSCs was promoted in the GLE-treated SF-CM group. ADSC migration was stimulated by upregulating the levels of α-smooth muscle actin, collagen type I alpha 2, and vascular endothelial growth factor expression through the PI3K/AKT pathway. Those results indicate that GLE can exert regenerative ability by regulating fibroblasts, and adipocyte interactions, improving cellular senescence. We conducted a clinical trial of subjects over 45 years of age to confirm the anti-ageing effects of GLE in vivo and observed changes in ageing parameters, such as skin wrinkles and volume on the face (IRB No. DM-IRB-2023-809-01-T1). The results showed that GLE-containing cream was more effective in improving skin wrinkles, elasticity, density, thickness, and volume around sunken eyes after 4 weeks of use than placebo. In conclusion, GLE plays an important role in inhibiting the ageing transition to ADSCs by inhibiting the senescence of fibroblasts and can be a promising anti-ageing strategy.
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Affiliation(s)
- Jieun Woo
- BioSpectrum Life Science Institute, A1805, U-TOWER, 767, Yongin, Republic of Korea
| | - Hyanggi Ji
- BioSpectrum Life Science Institute, A1805, U-TOWER, 767, Yongin, Republic of Korea
| | - Kyungeun Jeon
- BioSpectrum Life Science Institute, A1805, U-TOWER, 767, Yongin, Republic of Korea
| | - Hongbae Kim
- BioSpectrum Life Science Institute, A1805, U-TOWER, 767, Yongin, Republic of Korea
| | - Sohyun Yoon
- Dermacle Inc., A1606, U-TOWER, 767, Yongin, Republic of Korea
| | - Yunhee Hwang
- Dermacle Inc., A1606, U-TOWER, 767, Yongin, Republic of Korea
| | - Eunae Cho
- BioSpectrum Life Science Institute, A1805, U-TOWER, 767, Yongin, Republic of Korea
| | - Deokhoon Park
- BioSpectrum Life Science Institute, A1805, U-TOWER, 767, Yongin, Republic of Korea
| | - Eunsun Jung
- BioSpectrum Life Science Institute, A1805, U-TOWER, 767, Yongin, Republic of Korea
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Roato I, Visca M, Mussano F. Suppressing the Aging Phenotype of Mesenchymal Stromal Cells: Are We Ready for Clinical Translation? Biomedicines 2024; 12:2811. [PMID: 39767719 PMCID: PMC11673080 DOI: 10.3390/biomedicines12122811] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2024] [Revised: 12/06/2024] [Accepted: 12/09/2024] [Indexed: 01/11/2025] Open
Abstract
Mesenchymal stem/stromal cells (MSCs) are involved in the maintenance and regeneration of a large variety of tissues due to their stemness and multi-lineage differentiation capability. Harnessing these advantageous features, a flurry of clinical trials have focused on MSCs to treat different pathologies, but only few protocols have received regulatory approval so far. Among the various causes hindering MSCs' efficacy is the emergence of cellular senescence, which has been correlated with specific characteristics, such as morphological and epigenetic alterations, DNA damage, ROS production, mitochondrial dysfunction, telomere shortening, non-coding RNAs, loss of proteostasis, and a peculiar senescence-associated secretory phenotype. Several strategies have been investigated for delaying or even hopefully reverting the onset of senescence, as assessed by the senescent phenotype of MSCs. Here, the authors reviewed the most updated literature on the potential causes of senescence, with a particular emphasis on the current and future therapeutic approaches aimed at reverting senescence and/or extending the functional lifespan of stem cells.
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Affiliation(s)
- Ilaria Roato
- Department of Surgical Sciences, CIR-Dental School, University of Turin, 10126 Turin, Italy; (M.V.); (F.M.)
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Gu K, Feng XM, Sun SQ, Hao XY, Wen Y. Yes-associated protein-mediated melatonin regulates the function of periodontal ligament stem cells under oxidative stress conditions. World J Stem Cells 2024; 16:926-943. [DOI: 10.4252/wjsc.v16.i11.926] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Revised: 08/20/2024] [Accepted: 09/06/2024] [Indexed: 11/26/2024] Open
Abstract
BACKGROUND Human periodontal ligament stem cells (PDLSCs) regenerate oral tissue. In vitro expansion causes replicative senescence in stem cells. This causes intracellular reactive oxygen species (ROS) accumulation, which can impair stem cell function. Tissue engineering efficiency is reduced by exogenous ROS stimulation, which causes premature senescence under oxidative stress. Melatonin (MT), a powerful free radical scavenger, can delay PDLSCs senescence but may not maintain stemness under oxidative stress. This experiment examined the effects of hydrogen peroxide-induced oxidative stress on PDLSCs’ apoptosis, senescence, and stemness.
AIM To determine if MT can reverse the above effects along with the underlying molecular mechanisms involved.
METHODS PDLSCs were isolated from human premolars and cultured in different conditions. Flow cytometry was used to characterize the cell surface markers of PDLSCs. Hydrogen peroxide was used to induce oxidative stress in PDLSCs. Cell cycle, proliferation, apoptosis, differentiation, ROS, and senescence-associated β-galactosidase activity were assessed by various assays. Reverse transcription-polymerase chain reaction and western blot were used to measure the expression of genes and proteins related to stemness and senescence.
RESULTS MT increases Yes-associated protein expression and maintains cell stemness in an induced inflammatory microenvironment, which may explain its therapeutic effects. We examined how MT affects PDLSCs aging and stemness and its biological mechanisms.
CONCLUSION Our study reveals MT’s role in regulating oxidative stress in PDLSCs and Yes-associated protein-mediated activity, providing insights into cellular functions and new therapeutic targets for tissue regeneration.
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Affiliation(s)
- Ke Gu
- Department of Implantology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, No. 44-1 Wenhua Road West, Jinan 250012, Shandong Province, China
- Stomatological Hospital, School of Medicine, Nankai University, Tianjin Key Laboratory of Oral and Maxillofacial Function Reconstruction, Tianjin 300041, China
| | - Xiao-Mei Feng
- Department of Implantology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, No. 44-1 Wenhua Road West, Jinan 250012, Shandong Province, China
| | - Shao-Qing Sun
- Department of Implantology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, No. 44-1 Wenhua Road West, Jinan 250012, Shandong Province, China
| | - Xing-Yao Hao
- Department of Implantology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, No. 44-1 Wenhua Road West, Jinan 250012, Shandong Province, China
| | - Yong Wen
- Department of Implantology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, No. 44-1 Wenhua Road West, Jinan 250012, Shandong Province, China
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7
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Shan XQ, Zhao L. Enhancing the functionality of mesenchymal stem cells: An attractive treatment strategy for metabolic dysfunction-associated steatotic liver disease? World J Stem Cells 2024; 16:854-859. [PMID: 39493827 PMCID: PMC11525648 DOI: 10.4252/wjsc.v16.i10.854] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2024] [Revised: 09/06/2024] [Accepted: 10/08/2024] [Indexed: 10/25/2024] Open
Abstract
The intrinsic heterogeneity of metabolic dysfunction-associated fatty liver disease (MASLD) and the intricate pathogenesis have impeded the advancement and clinical implementation of therapeutic interventions, underscoring the critical demand for novel treatments. A recent publication by Li et al proposes mesenchymal stem cells as promising effectors for the treatment of MASLD. This editorial is a continuum of the article published by Jiang et al which focuses on the significance of strategies to enhance the functionality of mesenchymal stem cells to improve efficacy in curing MASLD, including physical pretreatment, drug or chemical pretreatment, pretreatment with bioactive substances, and genetic engineering.
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Affiliation(s)
- Xiao-Qian Shan
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin 300381, China
| | - Lan Zhao
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin 300381, China.
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Cai W, Xiao Y, Yan J, Peng H, Tu C. EMF treatment delays mesenchymal stem cells senescence during long-term in vitro expansion by modulating autophagy. Front Cell Dev Biol 2024; 12:1489774. [PMID: 39435332 PMCID: PMC11491334 DOI: 10.3389/fcell.2024.1489774] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2024] [Accepted: 09/24/2024] [Indexed: 10/23/2024] Open
Abstract
Introduction Bone marrow mesenchymal stem cells (BMSCs) are widely used in tissue engineering and regenerative medicine as seed cells. Due to low amount in bone marrow, BMSCs must be expanded and cultured in vitro before application. However, the senescence of stem cell caused by long-term in vitro culture greatly limits its efficacy of transplantation. Methods In this study, we propose an approach based on electromagnetic fields (EMF) treatment to rejuvenate aged BMSCs due to long-term in vitro culture. Aged BMSCs were treated with sinusoidal EMF (50 Hz, 0.4 mT), and stem cell senescence, cell proliferation, cell differentiation, cell stemness and autophagy level were detected. Additionally, aged BMSCs-laden hydrogels were transplanted into the rat critical-sized calvarial defect with or without EMF treatment. The bone formation was evaluated 8 weeks after surgery. Results Our results indicated that the BMSCs age significantly after long-term in vitro passaging. The self-renew, multiple differentiation capacity, senescence phenotypes and stemness of aged BMSCs are partly reversed by EMF treatment with a frequency of 50 Hz and strength of 0.4 mT. Moreover, declined autophagy level is observed in BMSCs during long-term in vitro passaging and BMSCs senescence is closely associated with autophagy regulation. Additionally, the mechanistic investigation reveals that EMF treatment rejuvenate senescent BMSCs by enhancing autophagy. Furthermore, EMF treatment significantly promote the therapeutic effect of long-term passaged BMSCs on bone formation in vivo. Conclusion Overall, our study identifies a practical approach for the rejuvenation of old BMSCs and may provide a promising candidate in tissue engineering and stem cell therapy.
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Affiliation(s)
- Wenxiang Cai
- Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Yifan Xiao
- Department of Pathology and Pathophysiology, School of Medicine, Jianghan University, Wuhan, Hubei, China
- Hubei Key Laboratory of Cognitive and Affective Disorders, School of Medicine, Institute of Biomedical Sciences, Jianghan University, Wuhan, Hubei, China
| | - Jiyuan Yan
- Department of Orthopedics, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China
| | - Hao Peng
- Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Chang Tu
- Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
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Jiang H, Chen J, Lin Z, Liao N. Melatonin enhances therapeutic outcomes of adipose tissue-derived mesenchymal stem cell therapy in rat osteoarthritis by reducing TNF-α and IL-1β-induced injuries. Cytotechnology 2024; 76:547-558. [PMID: 39188645 PMCID: PMC11344747 DOI: 10.1007/s10616-024-00635-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2024] [Accepted: 05/03/2024] [Indexed: 08/28/2024] Open
Abstract
Although adipose tissue-derived mesenchymal stem cell (ADSC) transplantation has been effectively used to treat osteoarthritis (OA), the low cell survival rate induced by the inflammatory and oxidative stress, severely affects the therapeutic efficiency of ADSC transplantation in OA. This study was designed to evaluate whether melatonin pretreatment could improve ADSC survival and its therapeutic efficacy in OA. The papain-induced OA rats were pretreated with melatonin via intra-articular injection and then intra-articular injected with indocyanine green (ICG)-labeled ADSCs (3 × 106/rat). Afterward, ADSC retention was evaluated by NIR-II fluorescence imaging. The tibia and synovial fluid were collected for histopathological examination and ELISA assay, respectively. To confirm the anti-inflammatory effect of melatonin, a TNF-α and IL-1β-induced cell model was used to evaluate the protective effects of melatonin on ADSC viability, cell apoptosis, and migration. Our results showed that melatonin pretreatment enhanced ADSC survival and improved the therapeutic effects of ADSC transplantation on cartilage repair, and anti-inflammation by reducing TNF-α, IL-6, IL-1β, and IL-12 in vivo. In particular, we also found that melatonin promoted ADSC viability and migration, and reduced cell apoptosis in vitro. In conclusion, this study supports that melatonin pretreatment can effectively improve ADSC survival and therapeutic efficiency in OA by reducing inflammatory injuries, which provides a novel strategy for enhancing ADSC therapy.
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Affiliation(s)
- Hao Jiang
- Department of Pain Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350000 People’s Republic of China
- National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212 People’s Republic of China
| | - Jiafang Chen
- Department of Pain Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350000 People’s Republic of China
- National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212 People’s Republic of China
| | - Zhangya Lin
- Department of Neurosurgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350000 People’s Republic of China
- National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212 People’s Republic of China
| | - Naishun Liao
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025 People’s Republic of China
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Matuszewska J, Krawiec A, Radziemski A, Uruski P, Tykarski A, Mikuła-Pietrasik J, Książek K. Alterations of receptors and insulin-like growth factor binding proteins in senescent cells. Eur J Cell Biol 2024; 103:151438. [PMID: 38945074 DOI: 10.1016/j.ejcb.2024.151438] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2024] [Revised: 06/24/2024] [Accepted: 06/25/2024] [Indexed: 07/02/2024] Open
Abstract
The knowledge about cellular senescence expands dynamically, providing more and more conclusive evidence of its triggers, mechanisms, and consequences. Senescence-associated secretory phenotype (SASP), one of the most important functional traits of senescent cells, is responsible for a large extent of their context-dependent activity. Both SASP's components and signaling pathways are well-defined. A literature review shows, however, that a relatively underinvestigated aspect of senescent cell autocrine and paracrine activity is the change in the production of proteins responsible for the reception and transmission of SASP signals, i.e., receptors and binding proteins. For this reason, we present in this article the current state of knowledge regarding senescence-associated changes in cellular receptors and insulin-like growth factor binding proteins. We also discuss the role of these alterations in senescence induction and maintenance, pro-cancerogenic effects of senescent cells, and aging-related structural and functional malfunctions.
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Affiliation(s)
- Julia Matuszewska
- Poznan University of Medical Sciences, Department of Pathophysiology of Ageing and Civilization Diseases, Święcickiego 4 Str., Poznań 60-781, Poland
| | - Adrianna Krawiec
- Poznan University of Medical Sciences, Department of Pathophysiology of Ageing and Civilization Diseases, Święcickiego 4 Str., Poznań 60-781, Poland
| | - Artur Radziemski
- Poznan University of Medical Sciences, Department of Hypertensiology, Długa 1/2 Str., Poznań 61-848, Poland
| | - Paweł Uruski
- Poznan University of Medical Sciences, Department of Hypertensiology, Długa 1/2 Str., Poznań 61-848, Poland
| | - Andrzej Tykarski
- Poznan University of Medical Sciences, Department of Hypertensiology, Długa 1/2 Str., Poznań 61-848, Poland
| | - Justyna Mikuła-Pietrasik
- Poznan University of Medical Sciences, Department of Pathophysiology of Ageing and Civilization Diseases, Święcickiego 4 Str., Poznań 60-781, Poland
| | - Krzysztof Książek
- Poznan University of Medical Sciences, Department of Pathophysiology of Ageing and Civilization Diseases, Święcickiego 4 Str., Poznań 60-781, Poland.
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11
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Wei Y, Mou S, Yang Q, Liu F, Cooper ME, Chai Z. To target cellular senescence in diabetic kidney disease: the known and the unknown. Clin Sci (Lond) 2024; 138:991-1007. [PMID: 39139135 PMCID: PMC11327223 DOI: 10.1042/cs20240717] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2024] [Revised: 07/07/2024] [Accepted: 07/29/2024] [Indexed: 08/15/2024]
Abstract
Cellular senescence represents a condition of irreversible cell cycle arrest, characterized by heightened senescence-associated beta-galactosidase (SA-β-Gal) activity, senescence-associated secretory phenotype (SASP), and activation of the DNA damage response (DDR). Diabetic kidney disease (DKD) is a significant contributor to end-stage renal disease (ESRD) globally, with ongoing unmet needs in terms of current treatments. The role of senescence in the pathogenesis of DKD has attracted substantial attention with evidence of premature senescence in this condition. The process of cellular senescence in DKD appears to be associated with mitochondrial redox pathways, autophagy, and endoplasmic reticulum (ER) stress. Increasing accumulation of senescent cells in the diabetic kidney not only leads to an impaired capacity for repair of renal injury, but also the secretion of pro-inflammatory and profibrotic cytokines and growth factors causing inflammation and fibrosis. Current treatments for diabetes exhibit varying degrees of renoprotection, potentially via mitigation of senescence in the diabetic kidney. Targeting senescent cell clearance through pharmaceutical interventions could emerge as a promising strategy for preventing and treating DKD. In this paper, we review the current understanding of senescence in DKD and summarize the possible therapeutic interventions relevant to senescence in this field.
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Affiliation(s)
- Yuehan Wei
- Department of Diabetes, School of Translational Medicine, Monash University, Melbourne, Australia
- Department of Nephrology, Molecular Cell Laboratory for Kidney Disease, Shanghai Peritoneal Dialysis Research Center, Ren Ji Hospital, Uremia Diagnosis and Treatment Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Shan Mou
- Department of Nephrology, Molecular Cell Laboratory for Kidney Disease, Shanghai Peritoneal Dialysis Research Center, Ren Ji Hospital, Uremia Diagnosis and Treatment Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qing Yang
- Department of Nephrology, Laboratory of Diabetic Kidney Disease, Kidney Research Institute, West China Hospital, Sichuan University, Chengdu, China
| | - Fang Liu
- Department of Nephrology, Laboratory of Diabetic Kidney Disease, Kidney Research Institute, West China Hospital, Sichuan University, Chengdu, China
| | - Mark E Cooper
- Department of Diabetes, School of Translational Medicine, Monash University, Melbourne, Australia
| | - Zhonglin Chai
- Department of Diabetes, School of Translational Medicine, Monash University, Melbourne, Australia
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12
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Wang J, Zhang M, Wang H. Emerging Landscape of Mesenchymal Stem Cell Senescence Mechanisms and Implications on Therapeutic Strategies. ACS Pharmacol Transl Sci 2024; 7:2306-2325. [PMID: 39144566 PMCID: PMC11320744 DOI: 10.1021/acsptsci.4c00284] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2024] [Revised: 07/05/2024] [Accepted: 07/09/2024] [Indexed: 08/16/2024]
Abstract
Mesenchymal stem cells (MSCs) hold significant promise for regenerative medicine and tissue engineering due to their unique multipotent differentiation ability and immunomodulatory properties. MSC therapy is widely discussed and utilized in clinical treatment. However, during both in vitro expansion and in vivo transplantation, MSCs are prone to senescence, an irreversible growth arrest characterized by morphological, gene expression, and functional changes in genomic regulation. The microenvironment surrounding MSCs plays a crucial role in modulating their senescence phenotype, influenced by factors such as hypoxia, inflammation, and aging status. Numerous strategies targeting MSC senescence have been developed, including senolytics and senomorphic agents, antioxidant and exosome therapies, mitochondrial transfer, and niche modulation. Novel approaches addressing replicative senescence have also emerged. This paper comprehensively reviews the current molecular manifestations of MSC senescence, addresses the environmental impact on senescence, and highlights potential therapeutic strategies to mitigate senescence in MSC-based therapies. These insights aim to enhance the efficacy and understanding of MSC therapies.
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Affiliation(s)
- Jing Wang
- Department
of Cellular and Molecular Medicine, University
of California San Diego, 9500 Gilman Drive, La Jolla, California 92093, United States
| | - Muqing Zhang
- Institute
of Cell Engineering, School of Medicine, Johns Hopkins University, Baltimore, Maryland, 21215, United States
| | - Hu Wang
- Institute
of Cell Engineering, School of Medicine, Johns Hopkins University, Baltimore, Maryland, 21215, United States
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13
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Chen E, Wang T, Sun Z, Gu Z, Xiao S, Ding Y. Polyphenols-based intelligent oral barrier membranes for periodontal bone defect reconstruction. Regen Biomater 2024; 11:rbae058. [PMID: 38854682 PMCID: PMC11157154 DOI: 10.1093/rb/rbae058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Revised: 05/04/2024] [Accepted: 05/10/2024] [Indexed: 06/11/2024] Open
Abstract
Periodontitis-induced periodontal bone defects significantly impact patients' daily lives. The guided tissue regeneration and guided bone regeneration techniques, which are based on barrier membranes, have brought hope for the regeneration of periodontal bone defects. However, traditional barrier membranes lack antimicrobial properties and cannot effectively regulate the complex oxidative stress microenvironment in periodontal bone defect areas, leading to unsatisfactory outcomes in promoting periodontal bone regeneration. To address these issues, our study selected the collagen barrier membrane as the substrate material and synthesized a novel barrier membrane (PO/4-BPBA/Mino@COL, PBMC) with an intelligent antimicrobial coating through a simple layer-by-layer assembly method, incorporating reactive oxygen species (ROS)-scavenging components, commercial dual-functional linkers and antimicrobial building blocks. Experimental results indicated that PBMC exhibited good degradability, hydrophilicity and ROS-responsiveness, allowing for the slow and controlled release of antimicrobial drugs. The outstanding antibacterial, antioxidant and biocompatibility properties of PBMC contributed to resistance to periodontal pathogen infection and regulation of the oxidative balance, while enhancing the migration and osteogenic differentiation of human periodontal ligament stem cells. Finally, using a rat periodontal bone defect model, the therapeutic effect of PBMC in promoting periodontal bone regeneration under infection conditions was confirmed. In summary, the novel barrier membranes designed in this study have significant potential for clinical application and provide a reference for the design of future periodontal regenerative functional materials.
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Affiliation(s)
- Enni Chen
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
- Department of Periodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Tianyou Wang
- College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu 610065, China
| | - Zhiyuan Sun
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
- Department of Periodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Zhipeng Gu
- College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu 610065, China
| | - Shimeng Xiao
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
- Department of Periodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Yi Ding
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
- Department of Periodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
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14
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Behtaj D, Ghorbani A, Eslamian G, Malekpour Alamdari N, Abbasi M, Zand H, Shakery A, Shimi G, Sohouli MH, Fazeli Taherian S. Ex vivo Anti-Senescence Activity of N-Acetylcysteine in Visceral Adipose Tissue of Obese Volunteers. Obes Facts 2024; 17:355-363. [PMID: 38718763 PMCID: PMC11299969 DOI: 10.1159/000539255] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2023] [Accepted: 05/06/2024] [Indexed: 08/07/2024] Open
Abstract
INTRODUCTION Excessive visceral adiposity is known to drive the onset of metabolic derangements, mostly involving oxidative stress, prolonged inflammation, and cellular senescence. N-acetylcysteine (NAC) is a synthetic form of l-cysteine with potential antioxidant, anti-inflammatory, and anti-senescence properties. This ex-vivo study aimed to determine the effect of NAC on some markers of senescence including β-galactosidase activity and p16, p53, p21, IL-6, and TNF-α gene expressions in visceral adipose tissue in obese adults. METHODS This ex-vivo experimental study involved 10 obese participants who were candidates for bariatric surgery. Duplicate biopsies from the abdominal visceral adipose tissue were obtained from the omentum. The biopsies were treated with or without NAC (5 and 10 mm). To evaluate adipose tissue senescence, beta-galactosidase (β-gal) activity and the expression of P16, P21, P53, IL-6, and TNF-α were determined. ANOVA test was employed to analyze the varying markers of cellular senescence and inflammation between treatment groups. RESULTS The NAC at concentrations of 5 mm and 10 mm resulted in a noteworthy reduction β-gal activity compared to the control group (p < 0.001). Additionally, the expression of P16, P21, and IL-6 was significantly reduced following treatment with NAC (5 mm) and NAC (10 mm) compared to the control group (All p < 0.001). DISCUSSION/CONCLUSION Taken together, these data suggest the senotherapeutic effect of NAC, as it effectively reduces the activity of SA-β-gal and the expression of IL-6, P16, and P21 genes in the visceral adipose tissue of obese individuals.
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Affiliation(s)
- Diba Behtaj
- Department of Cellular and Molecular Nutrition, Faculty of Nutrition and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Arman Ghorbani
- Department of Cellular and Molecular Nutrition, Faculty of Nutrition and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ghazaleh Eslamian
- Department of Cellular and Molecular Nutrition, Faculty of Nutrition and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Nasser Malekpour Alamdari
- School of Medicine, Department of General Surgery, Shahid Modarres Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Maryam Abbasi
- School of Medicine, Department of General Surgery, Shahid Modarres Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hamid Zand
- Department of Cellular and Molecular Nutrition, Faculty of Nutrition and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Azam Shakery
- Department of Cellular and Molecular Nutrition, Faculty of Nutrition and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ghazaleh Shimi
- Department of Cellular and Molecular Nutrition, Faculty of Nutrition and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Hasan Sohouli
- Department of Cellular and Molecular Nutrition, Faculty of Nutrition and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sepideh Fazeli Taherian
- Department of Cellular and Molecular Nutrition, Faculty of Nutrition and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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15
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Jiang N, Tian X, Wang Q, Hao J, Jiang J, Wang H. Regulation Mechanisms and Maintenance Strategies of Stemness in Mesenchymal Stem Cells. Stem Cell Rev Rep 2024; 20:455-483. [PMID: 38010581 DOI: 10.1007/s12015-023-10658-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/16/2023] [Indexed: 11/29/2023]
Abstract
Stemness pertains to the intrinsic ability of mesenchymal stem cells (MSCs) to undergo self-renewal and differentiate into multiple lineages, while simultaneously impeding their differentiation and preserving crucial differentiating genes in a state of quiescence and equilibrium. Owing to their favorable attributes, including uncomplicated isolation protocols, ethical compliance, and ease of procurement, MSCs have become a focal point of inquiry in the domains of regenerative medicine and tissue engineering. As age increases or ex vivo cultivation is prolonged, the functionality of MSCs decreases and their stemness gradually diminishes, thereby limiting their potential therapeutic applications. Despite the existence of several uncertainties surrounding the comprehension of MSC stemness, considerable advancements have been achieved in the clarification of the potential mechanisms that lead to stemness loss, as well as the associated strategies for stemness maintenance. This comprehensive review provides a systematic overview of the factors influencing the preservation of MSC stemness, the molecular mechanisms governing it, the strategies for its maintenance, and the therapeutic potential associated with stemness. Finally, we underscore the obstacles and prospective avenues in present investigations, providing innovative perspectives and opportunities for the preservation and therapeutic utilization of MSC stemness.
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Affiliation(s)
- Nizhou Jiang
- Central Hospital of Dalian University of Technology Department of Spine Surgery, Dalian, China
- The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Xiliang Tian
- The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Quanxiang Wang
- Hongqi Hospital Affiliated to Mudanjiang Medical University, Mudanjiang, China
| | - Jiayu Hao
- Central Hospital of Dalian University of Technology Department of Spine Surgery, Dalian, China
| | - Jian Jiang
- Central Hospital of Dalian University of Technology Department of Spine Surgery, Dalian, China.
| | - Hong Wang
- Central Hospital of Dalian University of Technology Department of Spine Surgery, Dalian, China.
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Krasnova O, Kovaleva A, Saveleva A, Kulakova K, Bystrova O, Martynova M, Domnina A, Sopova J, Neganova I. Mesenchymal stem cells lose the senescent phenotype under 3D cultivation. Stem Cell Res Ther 2023; 14:373. [PMID: 38111010 PMCID: PMC10729581 DOI: 10.1186/s13287-023-03599-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Accepted: 12/04/2023] [Indexed: 12/20/2023] Open
Abstract
BACKGROUND Three-dimensional (3D) cell culture is widely used in various fields of cell biology. In comparison to conventional two-dimensional (2D) cell culture, 3D cell culture facilitates a more accurate replication of the in vivo microenvironment, which is essential for obtaining more relevant results. The application of 3D cell culture techniques in regenerative medicine, particularly in mesenchymal stem cell (MSC)-based research, has been extensively studied. Many of these studies focus on the enhanced paracrine activity of MSCs cultured in 3D environments. However, few focus on the cellular processes that occur during 3D cultivation. METHODS In this work, we studied the changes occurring within 3D-cultured MSCs (3D-MSCs). Specifically, we examined the expression of numerous senescent-associated markers, the actin cytoskeleton structure, the architecture of the Golgi apparatus and the localization of mTOR, one of the main positive regulators of replicative senescence. In addition, we assessed whether the selective elimination of senescent cells occurs upon 3D culturing by using cell sorting based on autofluorescence. RESULTS Our findings indicate that 3D-MSCs were able to lose replicative senescence markers under 3D cell culture conditions. We observed changes in actin cytoskeleton structure, Golgi apparatus architecture and revealed that 3D cultivation leads to the nuclear localization of mTOR, resulting in a decrease in its active cytoplasmic form. Additionally, our findings provide evidence that 3D cell culture promotes the phenotypic reversion of senescent cell phenotype rather than their removal from the bulk population. CONCLUSION These novel insights into the biology of 3D-MSCs can be applied to research in regenerative medicine to overcome replicative senescence and MSC heterogeneity as they often pose significant concerns regarding safety and effectiveness for therapeutic purposes.
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Affiliation(s)
- O Krasnova
- Institute of Cytology, Russian Academy of Sciences, Saint-Petersburg, Russia.
| | - A Kovaleva
- Institute of Cytology, Russian Academy of Sciences, Saint-Petersburg, Russia
| | - A Saveleva
- Institute of Cytology, Russian Academy of Sciences, Saint-Petersburg, Russia
| | - K Kulakova
- Institute of Cytology, Russian Academy of Sciences, Saint-Petersburg, Russia
| | - O Bystrova
- Institute of Cytology, Russian Academy of Sciences, Saint-Petersburg, Russia
| | - M Martynova
- Institute of Cytology, Russian Academy of Sciences, Saint-Petersburg, Russia
| | - A Domnina
- Institute of Cytology, Russian Academy of Sciences, Saint-Petersburg, Russia
| | - J Sopova
- Institute of Cytology, Russian Academy of Sciences, Saint-Petersburg, Russia
| | - I Neganova
- Institute of Cytology, Russian Academy of Sciences, Saint-Petersburg, Russia
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17
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Wang Y, Shen X, Song S, Chen Y, Wang Y, Liao J, Chen N, Zeng L. Mesenchymal stem cell-derived exosomes and skin photoaging: From basic research to practical application. PHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE 2023; 39:556-566. [PMID: 37605539 DOI: 10.1111/phpp.12910] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Revised: 06/25/2023] [Accepted: 08/01/2023] [Indexed: 08/23/2023]
Abstract
BACKGROUND Skin photoaging is a condition caused by long-term exposure to ultraviolet irradiation, resulting in a variety of changes in the skin, such as capillary dilation, increased or absent pigmentation, dryness, sagging, and wrinkles. Stem cells possess a remarkable antioxidant capacity and the ability to proliferate, differentiate, and migrate, and their main mode of action is through paracrine secretion, with exosomes being the primary form of secretion. Stem cell-derived exosomes contain a variety of growth factors and cytokines and may have great potential to promote skin repair and delay skin ageing. METHODS This review focuses on the mechanisms of UV-induced skin photoaging, the research progress of stem cell exosomes against skin photoaging, emerging application approaches and limitations in the application of exosome therapy. RESULT Exosomes derived from various stem cells have the potential to prevent skin photoaging. CONCLUSION The combination with novel materials may be a key step for their practical application, which could be an important direction for future basic research and practical applications.
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Affiliation(s)
- Yihao Wang
- Center of Burn & Plastic and Wound Healing Surgery, Hengyang Medical School, The First Affiliated Hospital, University of South China, Hengyang, China
| | - Xu Shen
- Center of Burn & Plastic and Wound Healing Surgery, Hengyang Medical School, The First Affiliated Hospital, University of South China, Hengyang, China
| | - Shenghua Song
- Center of Burn & Plastic and Wound Healing Surgery, Hengyang Medical School, The First Affiliated Hospital, University of South China, Hengyang, China
| | - Yan Chen
- Center of Burn & Plastic and Wound Healing Surgery, Hengyang Medical School, The First Affiliated Hospital, University of South China, Hengyang, China
| | - Yiping Wang
- Center of Burn & Plastic and Wound Healing Surgery, Hengyang Medical School, The First Affiliated Hospital, University of South China, Hengyang, China
| | - Junlin Liao
- Center of Burn & Plastic and Wound Healing Surgery, Hengyang Medical School, The First Affiliated Hospital, University of South China, Hengyang, China
| | - Nian Chen
- Center of Burn & Plastic and Wound Healing Surgery, Hengyang Medical School, The First Affiliated Hospital, University of South China, Hengyang, China
| | - Li Zeng
- Center of Burn & Plastic and Wound Healing Surgery, Hengyang Medical School, The First Affiliated Hospital, University of South China, Hengyang, China
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18
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Soleimani M, Cheraqpour K, Koganti R, Djalilian AR. Cellular senescence and ophthalmic diseases: narrative review. Graefes Arch Clin Exp Ophthalmol 2023; 261:3067-3082. [PMID: 37079093 DOI: 10.1007/s00417-023-06070-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Revised: 03/21/2023] [Accepted: 04/11/2023] [Indexed: 04/21/2023] Open
Abstract
PURPOSE Cellular senescence is a state of permanent growth arrest whereby a cell reaches its replicative limit. However, senescence can also be triggered prematurely in certain stressors including radiation, oxidative stress, and chemotherapy. This stress-induced senescence has been studied in the context of promoting inflammation, tumor development, and several chronic degenerative diseases of aging. Emerging research has elucidated the role of senescence in various ocular diseases. METHODS The literature search was performed using PubMed with using the query (senescence OR aging) AND (eye disease OR ocular disease OR ophthalmic disease OR cornea OR glaucoma OR cataract OR retina) on October 20th, 2022. No time restriction was proposed. Articles were excluded if they were not referenced in English. RESULTS Overall, 51 articles regarding senescence and ocular diseases were found and summarized in this study. Several signaling pathways have been implicated in the development of senescence. Currently, senescence has been linked to various corneal and retinal pathologies, as well as cataract and glaucoma. Given the number of pathologies, senolytics, which are small molecules with the ability to selective targeting of senescent cells, can be used as therapeutic or prophylactic agents. CONCLUSIONS Senescence has been shown to underlie the pathogenesis of numerous ocular diseases. The overall literature on senescence and ocular disease is growing rapidly. There is an ongoing debate whether or not cellular senescence detected in experiments contributes in a significant way to diseases. Research on understanding the mechanism of senescence from ocular cells and tissues is just beginning. Multiple animal models are required to test potential senolytics. Currently, no studies exist to date which have demonstrated the benefits of senolytic therapies in human studies.
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Affiliation(s)
- Mohammad Soleimani
- Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran
- Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL, USA
- Cornea Service, Stem Cell Therapy and Corneal Tissue Engineering Laboratory, Illinois Eye and Ear Infirmary, 1855 W. Taylor Street, M/C 648, Chicago, IL, 60612, USA
| | - Kasra Cheraqpour
- Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Raghuram Koganti
- Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL, USA
| | - Ali R Djalilian
- Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL, USA.
- Cornea Service, Stem Cell Therapy and Corneal Tissue Engineering Laboratory, Illinois Eye and Ear Infirmary, 1855 W. Taylor Street, M/C 648, Chicago, IL, 60612, USA.
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19
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Mas-Bargues C. Mitochondria pleiotropism in stem cell senescence: Mechanisms and therapeutic approaches. Free Radic Biol Med 2023; 208:657-671. [PMID: 37739140 DOI: 10.1016/j.freeradbiomed.2023.09.019] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Revised: 09/10/2023] [Accepted: 09/18/2023] [Indexed: 09/24/2023]
Abstract
Aging is a complex biological process characterized by a progressive decline in cellular and tissue function, ultimately leading to organismal aging. Stem cells, with their regenerative potential, play a crucial role in maintaining tissue homeostasis and repair throughout an organism's lifespan. Mitochondria, the powerhouses of the cell, have emerged as key players in the aging process, impacting stem cell function and contributing to age-related tissue dysfunction. Here are discuss the mechanisms through which mitochondria influence stem cell fate decisions, including energy production, metabolic regulation, ROS signalling, and epigenetic modifications. Therefore, this review highlights the role of mitochondria in driving stem cell senescence and the subsequent impact on tissue function, leading to overall organismal aging and age-related diseases. Finally, we explore potential anti-aging therapies targeting mitochondrial health and discuss their implications for promoting healthy aging. This comprehensive review sheds light on the critical interplay between mitochondrial function, stem cell senescence, and organismal aging, offering insights into potential strategies for attenuating age-related decline and promoting healthy longevity.
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Affiliation(s)
- Cristina Mas-Bargues
- Freshage Research Group, Department of Physiology, Faculty of Medicine, University of Valencia, Centro de Investigación Biomédica en Red Fragilidad y Envejecimiento Saludable-Instituto de Salud Carlos III (CIBERFES-ISCIII), INCLIVA, 46010, Valencia, Spain.
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20
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Wang Y, Jin S, Luo D, He D, Yu M, Zhu L, Li Z, Chen L, Ding C, Wu X, Wu T, Huang W, Zhao X, Xu M, Xie Z, Liu Y. Prim-O-glucosylcimifugin ameliorates aging-impaired endogenous tendon regeneration by rejuvenating senescent tendon stem/progenitor cells. Bone Res 2023; 11:54. [PMID: 37872152 PMCID: PMC10593834 DOI: 10.1038/s41413-023-00288-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2023] [Revised: 08/16/2023] [Accepted: 08/17/2023] [Indexed: 10/25/2023] Open
Abstract
Adult tendon stem/progenitor cells (TSPCs) are essential for tendon maintenance, regeneration, and repair, yet they become susceptible to senescence with age, impairing the self-healing capacity of tendons. In this study, we employ a recently developed deep-learning-based efficacy prediction system to screen potential stemness-promoting and senescence-inhibiting drugs from natural products using the transcriptional signatures of stemness. The top-ranked candidate, prim-O-glucosylcimifugin (POG), a saposhnikovia root extract, could ameliorate TPSC senescent phenotypes caused by long-term passage and natural aging in rats and humans, as well as restore the self-renewal and proliferative capacities and tenogenic potential of aged TSPCs. In vivo, the systematic administration of POG or the local delivery of POG nanoparticles functionally rescued endogenous tendon regeneration and repair in aged rats to levels similar to those of normal animals. Mechanistically, POG protects TSPCs against functional impairment during both passage-induced and natural aging by simultaneously suppressing nuclear factor-κB and decreasing mTOR signaling with the induction of autophagy. Thus, the strategy of pharmacological intervention with the deep learning-predicted compound POG could rejuvenate aged TSPCs and improve the regenerative capacity of aged tendons.
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Affiliation(s)
- Yu Wang
- Laboratory of Biomimetic Nanomaterials, Department of Orthodontics, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology & Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health & NMPA Key Laboratory for Dental Materials & Translational Research Center for Orocraniofacial Stem Cells and Systemic Health, Beijing, 100081, China
| | - Shanshan Jin
- Laboratory of Biomimetic Nanomaterials, Department of Orthodontics, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology & Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health & NMPA Key Laboratory for Dental Materials & Translational Research Center for Orocraniofacial Stem Cells and Systemic Health, Beijing, 100081, China
| | - Dan Luo
- CAS Center for Excellence in Nanoscience, Beijing Key Laboratory of Micro-nano Energy and Sensor, Beijing Institute of Nanoenergy and Nanosystems, Chinese Academy of Sciences, Beijing, 101400, China
| | - Danqing He
- Laboratory of Biomimetic Nanomaterials, Department of Orthodontics, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology & Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health & NMPA Key Laboratory for Dental Materials & Translational Research Center for Orocraniofacial Stem Cells and Systemic Health, Beijing, 100081, China
| | - Min Yu
- Laboratory of Biomimetic Nanomaterials, Department of Orthodontics, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology & Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health & NMPA Key Laboratory for Dental Materials & Translational Research Center for Orocraniofacial Stem Cells and Systemic Health, Beijing, 100081, China
| | - Lisha Zhu
- Laboratory of Biomimetic Nanomaterials, Department of Orthodontics, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology & Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health & NMPA Key Laboratory for Dental Materials & Translational Research Center for Orocraniofacial Stem Cells and Systemic Health, Beijing, 100081, China
| | - Zixin Li
- Laboratory of Biomimetic Nanomaterials, Department of Orthodontics, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology & Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health & NMPA Key Laboratory for Dental Materials & Translational Research Center for Orocraniofacial Stem Cells and Systemic Health, Beijing, 100081, China
| | - Liyuan Chen
- Laboratory of Biomimetic Nanomaterials, Department of Orthodontics, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology & Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health & NMPA Key Laboratory for Dental Materials & Translational Research Center for Orocraniofacial Stem Cells and Systemic Health, Beijing, 100081, China
| | - Chengye Ding
- Laboratory of Biomimetic Nanomaterials, Department of Orthodontics, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology & Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health & NMPA Key Laboratory for Dental Materials & Translational Research Center for Orocraniofacial Stem Cells and Systemic Health, Beijing, 100081, China
| | - Xiaolan Wu
- Laboratory of Biomimetic Nanomaterials, Department of Orthodontics, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology & Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health & NMPA Key Laboratory for Dental Materials & Translational Research Center for Orocraniofacial Stem Cells and Systemic Health, Beijing, 100081, China
| | - Tianhao Wu
- Laboratory of Biomimetic Nanomaterials, Department of Orthodontics, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology & Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health & NMPA Key Laboratory for Dental Materials & Translational Research Center for Orocraniofacial Stem Cells and Systemic Health, Beijing, 100081, China
| | - Weiran Huang
- Peking University International Cancer Institute, Health Science Center, Peking University, Beijing, 100083, China
| | - Xuelin Zhao
- Department of Orthopedics, the Fourth Medical Center of PLA General Hospital, Beijing, 100048, China
| | - Meng Xu
- Department of Orthopedics, the Fourth Medical Center of PLA General Hospital, Beijing, 100048, China
| | - Zhengwei Xie
- Peking University International Cancer Institute, Health Science Center, Peking University, Beijing, 100083, China.
| | - Yan Liu
- Laboratory of Biomimetic Nanomaterials, Department of Orthodontics, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology & Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health & NMPA Key Laboratory for Dental Materials & Translational Research Center for Orocraniofacial Stem Cells and Systemic Health, Beijing, 100081, China.
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21
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Wang X, Ouyang L, Chen W, Cao Y, Zhang L. Efficient expansion and delayed senescence of hUC-MSCs by microcarrier-bioreactor system. Stem Cell Res Ther 2023; 14:284. [PMID: 37794520 PMCID: PMC10552362 DOI: 10.1186/s13287-023-03514-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Accepted: 09/25/2023] [Indexed: 10/06/2023] Open
Abstract
BACKGROUND Human umbilical cord mesenchymal stem cells (hUC-MSCs) are widely used in cell therapy due to their robust immunomodulatory and tissue regenerative capabilities. Currently, the predominant method for obtaining hUC-MSCs for clinical use is through planar culture expansion, which presents several limitations. Specifically, continuous cell passaging can lead to cellular aging, susceptibility to contamination, and an absence of process monitoring and control, among other limitations. To overcome these challenges, the technology of microcarrier-bioreactor culture was developed with the aim of ensuring the therapeutic efficacy of cells while enabling large-scale expansion to meet clinical requirements. However, there is still a knowledge gap regarding the comparison of biological differences in cells obtained through different culture methods. METHODS We developed a culture process for hUC-MSCs using self-made microcarrier and stirred bioreactor. This study systematically compares the biological properties of hUC-MSCs amplified through planar culture and microcarrier-bioreactor systems. Additionally, RNA-seq was employed to compare the differences in gene expression profiles between the two cultures, facilitating the identification of pathways and genes associated with cell aging. RESULTS The findings revealed that hUC-MSCs expanded on microcarriers exhibited a lower degree of cellular aging compared to those expanded through planar culture. Additionally, these microcarrier-expanded hUC-MSCs showed an enhanced proliferation capacity and a reduced number of cells in the cell cycle retardation period. Moreover, bioreactor-cultured cells differ significantly from planar cultures in the expression of genes associated with the cytoskeleton and extracellular matrix. CONCLUSIONS The results of this study demonstrate that our microcarrier-bioreactor culture method enhances the proliferation efficiency of hUC-MSCs. Moreover, this culture method exhibits the potential to delay the process of cell aging while preserving the essential stem cell properties of hUC-MSCs.
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Affiliation(s)
- Xia Wang
- State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, People's Republic of China
| | - Liming Ouyang
- State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, People's Republic of China.
| | - Wenxia Chen
- State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, People's Republic of China
| | - Yulin Cao
- Beijing Tang Yi Hui Kang Biomedical Technology Co., LTD, Beijing, 100032, People's Republic of China
| | - Lixin Zhang
- State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, People's Republic of China
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22
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Miller RC, Lee J, Kim YJ, Han HS, Kong H. In-drop thermal cycling of microcrystal assembly for senescence control (MASC) with minimal variation in efficacy. ADVANCED FUNCTIONAL MATERIALS 2023; 33:2302232. [PMID: 37901180 PMCID: PMC10611434 DOI: 10.1002/adfm.202302232] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/25/2023] [Indexed: 10/31/2023]
Abstract
The secretome from mesenchymal stem cells (MSCs) has recently gained attention for new therapeutics. However, clinical application requires in vitro cell manufacturing to attain enough cells. Unfortunately, this process often drives MSCs into a senescent state that drastically changes cellular secretion activities. Antioxidants are used to reverse and prevent the propagation of senescence; however, their activity is short-lived. Polymer-stabilized crystallization of antioxidants has been shown to improve bioactivity, but the broad crystal size distribution (CSD) significantly increases the efficacy variation. Efforts were made to crystalize drugs in microdroplets to narrow the CSD, but the fraction of drops containing at least one crystal can be as low as 20%. To this end, this study demonstrates that in-drop thermal cycling of hyaluronic acid-modified antioxidant crystals, named microcrystal assembly for senescence control (MASC), can drive the fraction of microdrops containing crystals to >86% while achieving significantly narrower CSDs (13±3μm) than in bulk (35±11μm). Therefore, this approach considerably improves the practicality of CSD-control in drops. In addition to exhibiting uniform release, MASC made with antioxidizing N-acetylcysteine extended the release time by 40%. MASC further improves the restoration of reactive oxygen species homeostasis in MSCs, thus minimizing cellular senescence and preserving desired secretion activities. We propose that MASC is broadly useful to controlling senescence of a wide array of therapeutic cells during biomanufacturing.
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Affiliation(s)
- Ryan C. Miller
- Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
| | - Jonghwi Lee
- Department of Chemical Engineering and Materials Science, Chung-Ang University, Seoul 06974, Korea
| | - Young Jun Kim
- Environmental Safety Group, Korea Institute of Science and Technology-Europe, Saarbrucken 66123, Germany
| | - Hee-Sun Han
- Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
- Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
| | - Hyunjoon Kong
- Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
- Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
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23
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Yu S, Yu S, Liu H, Liao N, Liu X. Enhancing mesenchymal stem cell survival and homing capability to improve cell engraftment efficacy for liver diseases. Stem Cell Res Ther 2023; 14:235. [PMID: 37667383 PMCID: PMC10478247 DOI: 10.1186/s13287-023-03476-4] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Accepted: 08/25/2023] [Indexed: 09/06/2023] Open
Abstract
Although mesenchymal stem cell (MSC) transplantation provides an alternative strategy for end-stage liver disease (ESLD), further widespread application of MSC therapy is limited owing to low cell engraftment efficiency. Improving cell engraftment efficiency plays a critical role in enhancing MSC therapy for liver diseases. In this review, we summarize the current status and challenges of MSC transplantation for ESLD. We also outline the complicated cell-homing process and highlight how low cell engraftment efficiency is closely related to huge differences in extracellular conditions involved in MSC homing journeys ranging from constant, controlled conditions in vitro to variable and challenging conditions in vivo. Improving cell survival and homing capabilities enhances MSC engraftment efficacy. Therefore, we summarize the current strategies, including hypoxic priming, drug pretreatment, gene modification, and cytokine pretreatment, as well as splenectomy and local irradiation, used to improve MSC survival and homing capability, and enhance cell engraftment and therapeutic efficiency of MSC therapy. We hope that this review will provide new insights into enhancing the efficiency of MSC engraftment in liver diseases.
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Affiliation(s)
- Shaoxiong Yu
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, People's Republic of China
- Mengchao Med-X Center, Fuzhou University, Fuzhou, 350116, People's Republic of China
- The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, 350025, People's Republic of China
| | - Saihua Yu
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, People's Republic of China
- Mengchao Med-X Center, Fuzhou University, Fuzhou, 350116, People's Republic of China
- The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, 350025, People's Republic of China
| | - Haiyan Liu
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, People's Republic of China
- Mengchao Med-X Center, Fuzhou University, Fuzhou, 350116, People's Republic of China
- The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, 350025, People's Republic of China
| | - Naishun Liao
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, People's Republic of China.
- Mengchao Med-X Center, Fuzhou University, Fuzhou, 350116, People's Republic of China.
- The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, 350025, People's Republic of China.
| | - Xiaolong Liu
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, People's Republic of China.
- Mengchao Med-X Center, Fuzhou University, Fuzhou, 350116, People's Republic of China.
- The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, 350025, People's Republic of China.
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24
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Wang Y, Cheng H, Wang T, Zhang K, Zhang Y, Kang X. Oxidative stress in intervertebral disc degeneration: Molecular mechanisms, pathogenesis and treatment. Cell Prolif 2023; 56:e13448. [PMID: 36915968 PMCID: PMC10472537 DOI: 10.1111/cpr.13448] [Citation(s) in RCA: 57] [Impact Index Per Article: 28.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Revised: 02/26/2023] [Accepted: 03/01/2023] [Indexed: 03/16/2023] Open
Abstract
Low back pain (LBP) is a leading cause of labour loss and disability worldwide, and it also imposes a severe economic burden on patients and society. Among symptomatic LBP, approximately 40% is caused by intervertebral disc degeneration (IDD). IDD is the pathological basis of many spinal degenerative diseases such as disc herniation and spinal stenosis. Currently, the therapeutic approaches for IDD mainly include conservative treatment and surgical treatment, neither of which can solve the problem from the root by terminating the degenerative process of the intervertebral disc (IVD). Therefore, further exploring the pathogenic mechanisms of IDD and adopting targeted therapeutic strategies is one of the current research hotspots. Among the complex pathophysiological processes and pathogenic mechanisms of IDD, oxidative stress is considered as the main pathogenic factor. The delicate balance between reactive oxygen species (ROS) and antioxidants is essential for maintaining the normal function and survival of IVD cells. Excessive ROS levels can cause damage to macromolecules such as nucleic acids, lipids, and proteins of cells, affect normal cellular activities and functions, and ultimately lead to cell senescence or death. This review discusses the potential role of oxidative stress in IDD to further understand the pathophysiological processes and pathogenic mechanisms of IDD and provides potential therapeutic strategies for the treatment of IDD.
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Affiliation(s)
- Yidian Wang
- Department of Joint Surgery, Honghui HospitalXi'an Jiaotong UniversityXi'anShaanxiChina
| | - Huiguang Cheng
- Department of Joint Surgery, Honghui HospitalXi'an Jiaotong UniversityXi'anShaanxiChina
| | - Tao Wang
- Department of Joint Surgery, Honghui HospitalXi'an Jiaotong UniversityXi'anShaanxiChina
| | - Kun Zhang
- Department of Joint Surgery, Honghui HospitalXi'an Jiaotong UniversityXi'anShaanxiChina
| | - Yumin Zhang
- Department of Joint Surgery, Honghui HospitalXi'an Jiaotong UniversityXi'anShaanxiChina
| | - Xin Kang
- Department of Joint Surgery, Honghui HospitalXi'an Jiaotong UniversityXi'anShaanxiChina
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25
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Agriesti F, Landini F, Tamma M, Pacelli C, Mazzoccoli C, Calice G, Ruggieri V, Capitanio G, Mori G, Piccoli C, Capitanio N. Bioenergetic profile and redox tone modulate in vitro osteogenesis of human dental pulp stem cells: new perspectives for bone regeneration and repair. Stem Cell Res Ther 2023; 14:215. [PMID: 37608350 PMCID: PMC10463344 DOI: 10.1186/s13287-023-03447-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2023] [Accepted: 08/10/2023] [Indexed: 08/24/2023] Open
Abstract
BACKGROUND Redox signaling and energy metabolism are known to be involved in controlling the balance between self-renewal and proliferation/differentiation of stem cells. In this study we investigated metabolic and redox changes occurring during in vitro human dental pulp stem cells (hDPSCs) osteoblastic (OB) differentiation and tested on them the impact of the reactive oxygen species (ROS) signaling. METHODS hDPSCs were isolated from dental pulp and subjected to alkaline phosphatase and alizarin red staining, q-RT-PCR, and western blotting analysis of differentiation markers to assess achievement of osteogenic/odontogenic differentiation. Moreover, a combination of metabolic flux analysis and confocal cyto-imaging was used to profile the metabolic phenotype and to evaluate the redox tone of hDPSCs. RESULTS In differentiating hDPSCs we observed the down-regulation of the mitochondrial respiratory chain complexes expression since the early phase of the process, confirmed by metabolic flux analysis, and a reduction of the basal intracellular peroxide level in its later phase. In addition, dampened glycolysis was observed, thereby indicating a lower energy-generating phenotype in differentiating hDPSCs. Treatment with the ROS scavenger Trolox, applied in the early-middle phases of the process, markedly delayed OB differentiation of hDPSCs assessed as ALP activity, Runx2 expression, mineralization capacity, expression of stemness and osteoblast marker genes (Nanog, Lin28, Dspp, Ocn) and activation of ERK1/2. In addition, the antioxidant partly prevented the inhibitory effect on cell metabolism observed following osteogenic induction. CONCLUSIONS Altogether these results provided evidence that redox signaling, likely mediated by peroxide species, influenced the stepwise osteogenic expansion/differentiation of hDPSCs and contributed to shape its accompanying metabolic phenotype changes thus improving their efficiency in bone regeneration and repair.
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Affiliation(s)
- Francesca Agriesti
- Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy
- Laboratory of Pre-Clinical and Translational Research, IRCCS-CROB, Referral Cancer Center of Basilicata, 85028 Rionero in Vulture, Italy
| | - Francesca Landini
- Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy
| | - Mirko Tamma
- Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy
| | - Consiglia Pacelli
- Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy
| | - Carmela Mazzoccoli
- Laboratory of Pre-Clinical and Translational Research, IRCCS-CROB, Referral Cancer Center of Basilicata, 85028 Rionero in Vulture, Italy
| | - Giovanni Calice
- Laboratory of Pre-Clinical and Translational Research, IRCCS-CROB, Referral Cancer Center of Basilicata, 85028 Rionero in Vulture, Italy
| | - Vitalba Ruggieri
- Laboratory of Pre-Clinical and Translational Research, IRCCS-CROB, Referral Cancer Center of Basilicata, 85028 Rionero in Vulture, Italy
- Clinical Pathology Unit, “Madonna delle Grazie’’ Hospital, Matera, Italy
| | - Giuseppe Capitanio
- Department of Translational Biomedicine and Neuroscience “DiBraiN”, University of Bari “Aldo Moro”, 70124 Bari, Italy
| | - Giorgio Mori
- Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy
| | - Claudia Piccoli
- Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy
| | - Nazzareno Capitanio
- Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy
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26
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Cen Y, Qi J, Chen L, Xia C, Zheng M, Liu Y, Lou G. Decreased miR-17-92 cluster correlates with senescence features, disrupted oxidative homeostasis, and impaired therapeutic efficacy of mesenchymal stem cells. Am J Physiol Cell Physiol 2023; 325:C443-C455. [PMID: 37366574 DOI: 10.1152/ajpcell.00515.2022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Revised: 06/23/2023] [Accepted: 06/23/2023] [Indexed: 06/28/2023]
Abstract
Aging and replicative cellular senescence are associated with the reduced therapeutic potential of mesenchymal stem cells (MSCs) on a variety of diseases. This study aimed to determine the mechanism in MSC senescence and further explore a modification strategy to reverse senescence-associated cell dysfunction to improve the therapeutic efficacy of MSCs on acute liver failure (ALF). We found that the adipose tissue-derived MSCs from old mice (oAMSCs) exhibited senescence phenotypes and showed reduced therapeutic efficacy in lipopolysaccharide and D-galactosamine-induced ALF, as shown by the increased hepatic necrosis, liver histology activity index scores, serum liver function indicator levels, and inflammatory cytokine levels. The expression of miR-17-92 cluster members, especially miR-17 and miR-20a, was obviously decreased in oAMSCs and replicatively senescent AMSCs, and was consistent with the decreased oncogene c-Myc level during AMSC senescence and may mediate c-Myc stemness addiction. Further experiments revealed that c-Myc-regulated miR-17-92 expression contributed to increased p21 expression and redox system dysregulation during AMSC senescence. Furthermore, modification of AMSCs with the two key miRNAs in the miR-17-92 cluster mentioned above reversed the senescence features of oAMSCs and restored the therapeutic effect of senescent AMSCs on ALF. In conclusion, the cellular miR-17-92 cluster level is correlated with AMSC senescence and can be used both as an index for evaluating and as a modification target for improving the therapeutic potential of AMSCs.NEW & NOTEWORTHY We reported for the first time that c-Myc-regulated miR-17-92 contributed to increased p21 expression and redox system dysregulation during AMSC senescence and was associated with the reduced therapeutic effects of senescent AMSCs on ALF. Moreover, modifying the expression of the miR-17-92 cluster members, especially miR-17 and/or miR-20a, could reverse AMSC senescence. Thus, miR-17-92 cluster can be used both as an index for evaluating and as a modification strategy for improving the therapeutic potential of AMSCs.
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Affiliation(s)
- Yelei Cen
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Jinjin Qi
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Liang Chen
- Thyroid Disease Diagnosis and Treatment Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Caixia Xia
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
- Department of Infectious Diseases, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Min Zheng
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Yanning Liu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Guohua Lou
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
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27
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Georgieva I, Tchekalarova J, Iliev D, Tzoneva R. Endothelial Senescence and Its Impact on Angiogenesis in Alzheimer's Disease. Int J Mol Sci 2023; 24:11344. [PMID: 37511104 PMCID: PMC10379128 DOI: 10.3390/ijms241411344] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Revised: 07/07/2023] [Accepted: 07/10/2023] [Indexed: 07/30/2023] Open
Abstract
Endothelial cells are constantly exposed to environmental stress factors that, above a certain threshold, trigger cellular senescence and apoptosis. The altered vascular function affects new vessel formation and endothelial fitness, contributing to the progression of age-related diseases. This narrative review highlights the complex interplay between senescence, oxidative stress, extracellular vesicles, and the extracellular matrix and emphasizes the crucial role of angiogenesis in aging and Alzheimer's disease. The interaction between the vascular and nervous systems is essential for the development of a healthy brain, especially since neurons are exceptionally dependent on nutrients carried by the blood. Therefore, anomalies in the delicate balance between pro- and antiangiogenic factors and the consequences of disrupted angiogenesis, such as misalignment, vascular leakage and disturbed blood flow, are responsible for neurodegeneration. The implications of altered non-productive angiogenesis in Alzheimer's disease due to dysregulated Delta-Notch and VEGF signaling are further explored. Additionally, potential therapeutic strategies such as exercise and caloric restriction to modulate angiogenesis and vascular aging and to mitigate the associated debilitating symptoms are discussed. Moreover, both the roles of extracellular vesicles in stress-induced senescence and as an early detection marker for Alzheimer's disease are considered. The intricate relationship between endothelial senescence and angiogenesis provides valuable insights into the mechanisms underlying angiogenesis-related disorders and opens avenues for future research and therapeutic interventions.
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Affiliation(s)
- Irina Georgieva
- Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Acad. George Bonchev, Str. Bl. 21, 1113 Sofia, Bulgaria
| | - Jana Tchekalarova
- Institute of Neurobiology, Bulgarian Academy of Sciences, Acad. George Bonchev, Str. Bl. 23, 1113 Sofia, Bulgaria
| | - Dimitar Iliev
- Institute of Molecular Biology, Bulgarian Academy of Sciences, Acad. George Bonchev, Str. Bl. 21, 1113 Sofia, Bulgaria
| | - Rumiana Tzoneva
- Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Acad. George Bonchev, Str. Bl. 21, 1113 Sofia, Bulgaria
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28
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Lee SS, Vũ TT, Weiss AS, Yeo GC. Stress-induced senescence in mesenchymal stem cells: Triggers, hallmarks, and current rejuvenation approaches. Eur J Cell Biol 2023; 102:151331. [PMID: 37311287 DOI: 10.1016/j.ejcb.2023.151331] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 06/04/2023] [Accepted: 06/05/2023] [Indexed: 06/15/2023] Open
Abstract
Mesenchymal stem cells (MSCs) have emerged as promising cell-based therapies in the treatment of degenerative and inflammatory conditions. However, despite accumulating evidence of the breadth of MSC functional potency, their broad clinical translation is hampered by inconsistencies in therapeutic efficacy, which is at least partly due to the phenotypic and functional heterogeneity of MSC populations as they progress towards senescence in vitro. MSC senescence, a natural response to aging and stress, gives rise to altered cellular responses and functional decline. This review describes the key regenerative properties of MSCs; summarises the main triggers, mechanisms, and consequences of MSC senescence; and discusses current cellular and extracellular strategies to delay the onset or progression of senescence, or to rejuvenate biological functions lost to senescence.
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Affiliation(s)
- Sunny Shinchen Lee
- Charles Perkins Centre, The University of Sydney, NSW 2006, Australia; School of Life and Environmental Sciences, The University of Sydney, NSW 2006, Australia
| | - Thu Thuy Vũ
- Vinmec Research Institute of Stem Cell and Gene Technology, Vinmec Healthcare System, Hanoi, Viet Nam
| | - Anthony S Weiss
- Charles Perkins Centre, The University of Sydney, NSW 2006, Australia; School of Life and Environmental Sciences, The University of Sydney, NSW 2006, Australia; Sydney Nano Institute, The University of Sydney, NSW 2006, Australia
| | - Giselle C Yeo
- Charles Perkins Centre, The University of Sydney, NSW 2006, Australia; School of Life and Environmental Sciences, The University of Sydney, NSW 2006, Australia.
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29
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Chen Q, Young L, Barsotti R. Mitochondria in cell senescence: A Friend or Foe? ADVANCES IN PROTEIN CHEMISTRY AND STRUCTURAL BIOLOGY 2023; 136:35-91. [PMID: 37437984 DOI: 10.1016/bs.apcsb.2023.02.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/14/2023]
Abstract
Cell senescence denotes cell growth arrest in response to continuous replication or stresses damaging DNA or mitochondria. Mounting research suggests that cell senescence attributes to aging-associated failing organ function and diseases. Conversely, it participates in embryonic tissue maturation, wound healing, tissue regeneration, and tumor suppression. The acute or chronic properties and microenvironment may explain the double faces of senescence. Senescent cells display unique characteristics. In particular, its mitochondria become elongated with altered metabolomes and dynamics. Accordingly, mitochondria reform their function to produce more reactive oxygen species at the cost of low ATP production. Meanwhile, destructed mitochondrial unfolded protein responses further break the delicate proteostasis fostering mitochondrial dysfunction. Additionally, the release of mitochondrial damage-associated molecular patterns, mitochondrial Ca2+ overload, and altered NAD+ level intertwine other cellular organelle strengthening senescence. These findings further intrigue researchers to develop anti-senescence interventions. Applying mitochondrial-targeted antioxidants reduces cell senescence and mitigates aging by restoring mitochondrial function and attenuating oxidative stress. Metformin and caloric restriction also manifest senescent rescuing effects by increasing mitochondria efficiency and alleviating oxidative damage. On the other hand, Bcl2 family protein inhibitors eradicate senescent cells by inducing apoptosis to facilitate cancer chemotherapy. This review describes the different aspects of mitochondrial changes in senescence and highlights the recent progress of some anti-senescence strategies.
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Affiliation(s)
- Qian Chen
- Philadelphia College of Osteopathic Medicine, Philadelphia, PA, United States.
| | - Lindon Young
- Philadelphia College of Osteopathic Medicine, Philadelphia, PA, United States
| | - Robert Barsotti
- Philadelphia College of Osteopathic Medicine, Philadelphia, PA, United States
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30
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Iqbal H, Naeem N, Haneef K, Salim A. Sulfasalazine and Chromotrope 2B reduce oxidative stress in murine bone marrow-derived mesenchymal stem cells. Mol Biol Rep 2023; 50:4119-4131. [PMID: 36877347 DOI: 10.1007/s11033-023-08321-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Accepted: 02/02/2023] [Indexed: 03/07/2023]
Abstract
BACKGROUND With advancing age of stem cells, dysregulation of various processes at the cellular level occurs, thereby decreasing their regeneration potential. One of the changes that occurs during the aging process is the accumulation of reactive oxygen species (ROS), which accelerates the processes of cellular senescence and cell death. The aim of this study is to evaluate two antioxidant compounds; Chromotrope 2B and Sulfasalazine, for their antioxidant effects on young and old rat bone marrow mesenchymal stem cells (MSCs). METHODS AND RESULTS Oxidative stress was induced in MSCs by 5 µM dexamethasone for 96 h and the cells were treated with Chromotrope 2B or Sulfasalazine, 50 µM each. The effects of antioxidant treatment following oxidative stress induction was evaluated by transcriptional profiling of genes involved in the oxidative stress and telomere maintenance. Expression levels of Cat, Gpx7, Sod1, Dhcr24, Idh1, and Txnrd2 were found to be increased in young MSCs (yMSCs) as a result of oxidative stress, while Duox2, Parp1, and Tert1 expression were found to be decreased as compared to the control. In old MSCs (oMSCs), the expressions of Dhcr24, Txnrd2, and Parp1 increased, while that of Duox2, Gpx7, Idh1, and Sod1 decreased following oxidative stress. In both MSC groups, Chromotrope 2B prompted decrease in the ROS generation before and after the induction of oxidative stress. In oMSCs, ROS content was significantly reduced in the Sulfasalazine treated group. CONCLUSION Our findings suggest that both Chromotrope 2B and Sulfasalazine possess the potential to reduce the ROS content in both age groups, though the latter was found to be more potent. These compounds can be used to precondition MSCs to enhance their regenerative potential for future cell-based therapeutics.
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Affiliation(s)
- Hana'a Iqbal
- Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan
| | - Nadia Naeem
- Dow University of Health Sciences, Karachi, Pakistan
| | - Kanwal Haneef
- Dr. Zafar H. Zaidi Center for Proteomics, University of Karachi, Karachi, 75270, Pakistan
| | - Asmat Salim
- Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan.
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Deng L, Gupta V, Abyadeh M, Chitranshi N, Pushpitha K, Wu Y, Gupta V, You Y, Paulo JA, Graham SL, Mirzaei M, Haynes PA. Oxidative Stress Induced Dysfunction of Protein Synthesis in 661W Mice Photoreceptor Cells. Proteomes 2023; 11:12. [PMID: 37092453 PMCID: PMC10123756 DOI: 10.3390/proteomes11020012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Revised: 03/17/2023] [Accepted: 03/22/2023] [Indexed: 04/05/2023] Open
Abstract
Photoreceptor cells are highly susceptible to oxidative-stress-induced damage due to their high metabolic rate. Oxidative stress plays a key role in driving pathological events in several different ocular diseases, which lead to retinal degeneration and ultimately blindness. A growing number of studies have been performed to understand downstream events caused by ROS induced oxidative stress in photoreceptor cells; however, the underlying mechanisms of ROS toxicity are not fully understood. To shed light on ROS induced downstream pathological events, we employed a tandem mass tag (TMT) labelling-based quantitative mass-spectrometric approach to determine proteome changes in 661W photoreceptor cells following oxidative stress induction via the application of different concentrations of H2O2 at different time points. Overall, 5920 proteins were identified and quantified, and 450 differentially expressed proteins (DEPs) were identified, which were altered in a dose and time dependent manner in all treatment groups compared to the control group. These proteins were involved in several biological pathways, including spliceosome and ribosome response, activated glutathione metabolism, decreased ECM-receptor interaction, oxidative phosphorylation, abnormally regulated lysosome, apoptosis, and ribosome biogenesis. Our results highlighted ECM receptor interaction, oxidative phosphorylation and spliceosome pathways as the major targets of oxidative stress that might mediate vascular dysfunction and cellular senescence.
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Affiliation(s)
- Liting Deng
- Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Macquarie Park, NSW 2109, Australia
| | - Vivek Gupta
- Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Macquarie Park, NSW 2109, Australia
| | | | - Nitin Chitranshi
- Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Macquarie Park, NSW 2109, Australia
| | - Kanishka Pushpitha
- Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Macquarie Park, NSW 2109, Australia
| | - Yunqi Wu
- Australian Proteome Analysis Facility, Macquarie University, Macquarie Park, NSW 2109, Australia
| | - Veer Gupta
- School of Medicine, Deakin University, Geelong, VIC 3220, Australia
| | - Yuyi You
- Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Macquarie Park, NSW 2109, Australia
| | - Joao A. Paulo
- Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
| | - Stuart L. Graham
- Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Macquarie Park, NSW 2109, Australia
| | - Mehdi Mirzaei
- Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Macquarie Park, NSW 2109, Australia
| | - Paul A. Haynes
- School of Natural Sciences, Macquarie University, Macquarie Park, NSW 2109, Australia
- Biomolecular Discovery Research Centre, Macquarie University, Macquarie Park, NSW 2109, Australia
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32
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Song WJ, Liu PP, Meng ZQ, Jie Ding S, Xia Li H. N-acetylcysteine promotes the proliferation of porcine adipose-derived stem cells during in vitro long-term expansion for cultured meat production. Food Res Int 2023; 166:112606. [PMID: 36914351 DOI: 10.1016/j.foodres.2023.112606] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Revised: 02/09/2023] [Accepted: 02/14/2023] [Indexed: 02/18/2023]
Abstract
Cultured meat is an efficient, safe and sustainable meat production technology. Adipose-derived stem cell (ADSC) is a promising cell type for cultured meat. In vitro, obtaining numerous of ADSCs is a pivotal step for cultured meat. In this research, we demonstrated that the proliferation and adipogenic differentiation of ADSCs significantly decreased during serial passage. Then, senescence β-galactosidase (SA-β-gal) staining showed that the positive rate of P9 ADSCs was 7.74-fold than P3 ADSCs. Subsequently, RNA sequencing (RNA-seq) was performed for P3 and P9 ADSCs and found that PI3K-AKT pathway was up-regulated, but cell cycle and DNA repair pathway were down-regulated in P9 ADSCs. Then, N-Acetylcysteine (NAC) was added during long-term expansion and showed that NAC enhanced the ADSCs proliferation and maintained adipogenic differentiation. Finally, RNA-seq was performed for P9 ADSCs cultured with or without NAC and showed that NAC restored the cell cycle and DNA repair pathway in P9 ADSCs. These results highlighted that NAC was an excellent supplement for large-scale expansion of porcine ADSCs for cultured meat.
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Affiliation(s)
- Wen-Juan Song
- College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China
| | - Pei-Pei Liu
- College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China
| | - Zi-Qing Meng
- College of Food Science and Technology, Nanjing Agricultural University National Center of Meat Quality and Safety Nanjing, MOST Key Laboratory of Meat Processing and Quality Control, MOE Key Laboratory of Meat Processing, MOA Nanjing 210095, China
| | - Shi- Jie Ding
- College of Food Science and Technology, Nanjing Agricultural University National Center of Meat Quality and Safety Nanjing, MOST Key Laboratory of Meat Processing and Quality Control, MOE Key Laboratory of Meat Processing, MOA Nanjing 210095, China
| | - Hui- Xia Li
- College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China.
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Ye P, Feng L, Zhang D, Li R, Wen Y, Tong X, Shi S, Dong C. Metformin Ameliorates D-Galactose-Induced Senescent Human Bone Marrow-Derived Mesenchymal Stem Cells by Enhancing Autophagy. Stem Cells Int 2023; 2023:1429642. [PMID: 37035446 PMCID: PMC10079386 DOI: 10.1155/2023/1429642] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2022] [Revised: 01/16/2023] [Accepted: 03/11/2023] [Indexed: 04/04/2023] Open
Abstract
Human bone marrow-derived mesenchymal stem cells (hBMSCs) are promising candidates for stem cell therapy in clinical trials. Applications of hBMSCs in clinical therapy are limited by cellular senescence due to long-term ex vivo expansion. Metformin, an oral hypoglycemic drug for type 2 diabetes, has been shown to have antiaging effects. However, the mechanisms of metformin in antiaging treatment remain controversial. Here, we used D-galactose (D-gal) to establish an appropriate model of senescent hBMSCs to explore the antiaging effects of metformin. Following metformin treatment with a low concentration range, senescence phenotypes induced by D-gal significantly changed, including generation of reactive oxygen species (ROS), loss of mitochondrial membrane potential (MMP), and cell cycle arrest. In contrast, no apparent change was found in unsenescent hBMSCs. Furthermore, the results show that activation of 5'AMP-activated protein kinase (AMPK) by metformin enhances cell autophagy in senescent hBMSCs. These findings suggest that metformin exerts antiaging function within the low concentration range by enhancing autophagy and exhibits potential benefits for clinical stem cell therapy by ameliorating the ex vivo replicative senescence of hBMSCs.
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Affiliation(s)
- Pingting Ye
- Department of Oncology, Shanghai East Hospital, School of Medicine, Shanghai Key Laboratory of Chemical Assessment and Sustainability, School of Chemical Science and Engineering, Tongji University, Shanghai 200120, China
| | - Lei Feng
- Department of Oncology, Shanghai East Hospital, School of Medicine, Shanghai Key Laboratory of Chemical Assessment and Sustainability, School of Chemical Science and Engineering, Tongji University, Shanghai 200120, China
| | - Dan Zhang
- Department of Oncology, Shanghai East Hospital, School of Medicine, Shanghai Key Laboratory of Chemical Assessment and Sustainability, School of Chemical Science and Engineering, Tongji University, Shanghai 200120, China
| | - Ruihao Li
- Department of Oncology, Shanghai East Hospital, School of Medicine, Shanghai Key Laboratory of Chemical Assessment and Sustainability, School of Chemical Science and Engineering, Tongji University, Shanghai 200120, China
| | - Yixuan Wen
- Department of Oncology, Shanghai East Hospital, School of Medicine, Shanghai Key Laboratory of Chemical Assessment and Sustainability, School of Chemical Science and Engineering, Tongji University, Shanghai 200120, China
| | - Xiaohan Tong
- Department of Oncology, Shanghai East Hospital, School of Medicine, Shanghai Key Laboratory of Chemical Assessment and Sustainability, School of Chemical Science and Engineering, Tongji University, Shanghai 200120, China
| | - Shuo Shi
- Department of Oncology, Shanghai East Hospital, School of Medicine, Shanghai Key Laboratory of Chemical Assessment and Sustainability, School of Chemical Science and Engineering, Tongji University, Shanghai 200120, China
| | - Chunyan Dong
- Department of Oncology, Shanghai East Hospital, School of Medicine, Shanghai Key Laboratory of Chemical Assessment and Sustainability, School of Chemical Science and Engineering, Tongji University, Shanghai 200120, China
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Li H, Liang X, Chen Y, Liu K, Fu X, Zhang C, Wang X, Yang J. Synergy of antioxidant and M2 polarization in polyphenol-modified konjac glucomannan dressing for remodeling wound healing microenvironment. Bioeng Transl Med 2023; 8:e10398. [PMID: 36925701 PMCID: PMC10013815 DOI: 10.1002/btm2.10398] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Revised: 06/13/2022] [Accepted: 08/22/2022] [Indexed: 11/07/2022] Open
Abstract
Effective skin wound healing and tissue regeneration remain a challenge. Excessive/chronic inflammation inhibits wound healing, leading to scar formation. Herein, we report a wound dressing composed of KGM-GA based on the natural substances konjac glucomannan (KGM) and gallic acid (GA) that accelerates wound healing without any additional drugs. An in vitro study showed that KGM-GA could not only stimulate macrophage polarization to the anti-inflammatory M2 phenotype but also decrease reactive oxygen species (ROS) levels, indicating excellent anti-inflammatory properties. Moreover, in vivo studies of skin wounds demonstrated that the KGM-GA dressing significantly improved wound healing by accelerating wound closure, collagen deposition, and angiogenesis. In addition, it was observed that KGM-GA regulated M2 polarization, reducing the production of intracellular ROS in the wound microenvironment, which was consistent with the in vitro experiments. Therefore, this study designed a multifunctional biomaterial with biological activity, providing a novel dressing for wound healing.
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Affiliation(s)
- Huiyang Li
- Tianjin Key Laboratory of Biomaterial ResearchInstitute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical CollegeTianjinChina
| | - Xiaoyu Liang
- Tianjin Key Laboratory of Biomaterial ResearchInstitute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical CollegeTianjinChina
| | - Youlu Chen
- Tianjin Key Laboratory of Biomaterial ResearchInstitute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical CollegeTianjinChina
| | - Kaijing Liu
- Tianjin Key Laboratory of Biomaterial ResearchInstitute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical CollegeTianjinChina
| | - Xue Fu
- Tianjin Key Laboratory of Biomaterial ResearchInstitute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical CollegeTianjinChina
| | - Chuangnian Zhang
- Tianjin Key Laboratory of Biomaterial ResearchInstitute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical CollegeTianjinChina
| | - Xiaoli Wang
- Tianjin Key Laboratory of Biomaterial ResearchInstitute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical CollegeTianjinChina
| | - Jing Yang
- Tianjin Key Laboratory of Biomaterial ResearchInstitute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical CollegeTianjinChina
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Azam M, Ghufran H, Tasneem S, Mehmood A, Malik K, Yousaf MA, Tarar MN, Akram SJ, Riazuddin S. Priming of adipose-derived stem cells with curcumin prior to cryopreservation preserves their functional potency: Towards an 'Off-the-shelf' therapy for burns. Cryobiology 2023; 110:69-78. [PMID: 36470459 DOI: 10.1016/j.cryobiol.2022.12.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Revised: 11/18/2022] [Accepted: 12/01/2022] [Indexed: 12/12/2022]
Abstract
Stem cells-based treatment for burn wounds require frozen cells as an off-the-shelf therapy; however, cryopreservation-induced oxidative stress resulted in post-thaw cell death or loss of cell functions, thus arrested their clinical practicality. Although antioxidant priming to stem cells increase their resistant to oxidative stress, but this strategy is still unexplored on cryopreserved cells. Herein, we investigated whether curcumin priming before cryopreservation could preserve the therapeutic potency of thawed stem cells. For this, unprimed and curcumin-primed adipose-derived stem cells (ASCs) were cryopreserved for one month. Post-thawing, cells were assessed for viability by trypan blue assay; metabolic activity by MTT assay; senescence by senescence-associated (SA)-β-galactosidase activity staining assay; migration by scratch healing assay and; mRNA expression by real-time PCR. Subsequently, the healing potential was examined by injecting cells around the wound periphery of acidic burn in rats. Post-healing, skin architecture was histologically examined. Results demonstrated that, curcumin-primed frozen cells (Cryo/Cur-ASCs) showed better post-thaw viability, metabolic activity, migration ability and lower percent of senescence comparative to unprimed frozen cells (Cryo/ASCs). Curcumin priming alleviated the oxidative damage by activating the ROS-reducing cellular antioxidant system as shown by the evident increase in GSH levels and upregulated mRNA expression of glutathione peroxidase (GPx), superoxide dismutases (SOD1, SOD2), and catalase (CAT). Further, invivo findings revealed that Cryo/Cur-ASCs-treated wounds exhibited earlier wound closure with an improved architecture comparative to Cryo/ASCs and depicted healing capacity almost similar to Fresh/ASCs. Our findings suggested that curcumin priming could be effective to alleviate the cryo-induced oxidative stress in post-thawed cells.
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Affiliation(s)
- Maryam Azam
- National Centre of Excellence in Molecular Biology, 87-West Canal Bank Road, University of the Punjab, Lahore, Pakistan
| | - Hafiz Ghufran
- National Centre of Excellence in Molecular Biology, 87-West Canal Bank Road, University of the Punjab, Lahore, Pakistan
| | - Saba Tasneem
- National Centre of Excellence in Molecular Biology, 87-West Canal Bank Road, University of the Punjab, Lahore, Pakistan
| | - Azra Mehmood
- National Centre of Excellence in Molecular Biology, 87-West Canal Bank Road, University of the Punjab, Lahore, Pakistan.
| | - Kausar Malik
- National Centre of Excellence in Molecular Biology, 87-West Canal Bank Road, University of the Punjab, Lahore, Pakistan
| | | | - Moazzam N Tarar
- Jinnah Burn and Reconstructive Surgery Centre, Lahore, Pakistan
| | | | - Sheikh Riazuddin
- National Centre of Excellence in Molecular Biology, 87-West Canal Bank Road, University of the Punjab, Lahore, Pakistan; Jinnah Burn and Reconstructive Surgery Centre, Lahore, Pakistan
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36
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Savvidou MG, Georgiopoulou I, Antoniou N, Tzima S, Kontou M, Louli V, Fatouros C, Magoulas K, Kolisis FN. Extracts from Chlorella vulgaris Protect Mesenchymal Stromal Cells from Oxidative Stress Induced by Hydrogen Peroxide. PLANTS (BASEL, SWITZERLAND) 2023; 12:361. [PMID: 36679074 PMCID: PMC9866266 DOI: 10.3390/plants12020361] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Revised: 12/31/2022] [Accepted: 01/03/2023] [Indexed: 06/17/2023]
Abstract
Microalgae as unicellular eukaryotic organisms demonstrate several advantages for biotechnological and biological applications. Natural derived microalgae products demand has increased in food, cosmetic and nutraceutical applications lately. The natural antioxidants have been used for attenuation of mitochondrial cell damage caused by oxidative stress. This study evaluates the in vitro protective effect of Chlorella vulgaris bioactive extracts against oxidative stress in human mesenchymal stromal/stem cells (MSCs). The classical solid-liquid and the supercritical extraction, using biomass of commercially available and laboratory cultivated C. vulgaris, are employed. Oxidative stress induced by 300 μM H2O2 reduces cell viability of MSCs. The addition of C. vulgaris extracts, with increased protein content compared to carbohydrates, to H2O2 treated MSCs counteracted the oxidative stress, reducing reactive oxygen species levels without affecting MSC proliferation. The supercritical extraction was the most efficient extraction method for carotenoids resulting in enhanced antioxidant activity. Pre-treatment of MSCs with C. vulgaris extracts mitigates the oxidative damage ensued by H2O2. Initial proteomic analysis of secretome from licensed (TNFα-activated) MSCs treated with algal extracts reveals a signature of differentially regulated proteins that fall into clinically relevant pathways such as inflammatory signaling. The enhanced antioxidative and possibly anti-inflammatory capacity could be explored in the context of future cell therapies.
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Affiliation(s)
- Maria G. Savvidou
- Biotechnology Laboratory, School of Chemical Engineering, National Technical University of Athens, Iroon Polytechniou Str., Zografou Campus, 15780 Athens, Greece
| | - Ioulia Georgiopoulou
- Laboratory of Thermodynamics and Transport Phenomena, School of Chemical Engineering, National Technical University of Athens, 9 Iroon Polytechniou Str., Zografou Campus, 15780 Athens, Greece
| | - Nasia Antoniou
- TheraCell Advanced Biotechnologies, 14564 Kifisia, Greece
| | - Soultana Tzima
- Laboratory of Thermodynamics and Transport Phenomena, School of Chemical Engineering, National Technical University of Athens, 9 Iroon Polytechniou Str., Zografou Campus, 15780 Athens, Greece
| | - Maria Kontou
- TheraCell Advanced Biotechnologies, 14564 Kifisia, Greece
| | - Vasiliki Louli
- Laboratory of Thermodynamics and Transport Phenomena, School of Chemical Engineering, National Technical University of Athens, 9 Iroon Polytechniou Str., Zografou Campus, 15780 Athens, Greece
| | | | - Kostis Magoulas
- Laboratory of Thermodynamics and Transport Phenomena, School of Chemical Engineering, National Technical University of Athens, 9 Iroon Polytechniou Str., Zografou Campus, 15780 Athens, Greece
| | - Fragiskos N. Kolisis
- Biotechnology Laboratory, School of Chemical Engineering, National Technical University of Athens, Iroon Polytechniou Str., Zografou Campus, 15780 Athens, Greece
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Rubin de Celis MF, Garcia-Martin R, Syed I, Lee J, Aguayo-Mazzucato C, Bonner-Weir S, Kahn BB. PAHSAs reduce cellular senescence and protect pancreatic beta cells from metabolic stress through regulation of Mdm2/p53. Proc Natl Acad Sci U S A 2022; 119:e2206923119. [PMID: 36375063 PMCID: PMC9704710 DOI: 10.1073/pnas.2206923119] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2022] [Accepted: 10/03/2022] [Indexed: 11/16/2022] Open
Abstract
Senescence in pancreatic beta cells plays a major role in beta cell dysfunction, which leads to impaired glucose homeostasis and diabetes. Therefore, prevention of beta cell senescence could reduce the risk of diabetes. Treatment of nonobese diabetic (NOD) mice, a model of type 1 autoimmune diabetes (T1D), with palmitic acid hydroxy stearic acids (PAHSAs), a novel class of endogenous lipids with antidiabetic and antiinflammatory effects, delays the onset and reduces the incidence of T1D from 82% with vehicle treatment to 35% with PAHSAs. Here, we show that a major mechanism by which PAHSAs protect islets of the NOD mice is by directly preventing and reversing the initial steps of metabolic stress-induced senescence. In vitro PAHSAs increased Mdm2 expression, which decreases the stability of p53, a key inducer of senescence-related genes. In addition, PAHSAs enhanced expression of protective genes, such as those regulating DNA repair and glutathione metabolism and promoting autophagy. We demonstrate the translational relevance by showing that PAHSAs prevent and reverse early stages of senescence in metabolically stressed human islets by the same Mdm2 mechanism. Thus, a major mechanism for the dramatic effect of PAHSAs in reducing the incidence of type 1 diabetes in NOD mice is decreasing cellular senescence; PAHSAs may have a similar benefit in humans.
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Affiliation(s)
- Maria F. Rubin de Celis
- Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215
| | | | - Ismail Syed
- Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215
| | - Jennifer Lee
- Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215
| | | | | | - Barbara B. Kahn
- Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215
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Pooled evidence from preclinical and clinical studies for stem cell-based therapy in ARDS and COVID-19. Mol Cell Biochem 2022; 478:1487-1518. [PMID: 36394787 DOI: 10.1007/s11010-022-04601-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2022] [Accepted: 10/24/2022] [Indexed: 11/18/2022]
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Naeimi A, Zaminy A, Amini N, Balabandi R, Golipoor Z. Effects of melatonin-pretreated adipose-derived mesenchymal stem cells (MSC) in an animal model of spinal cord injury. BMC Neurosci 2022; 23:65. [PMCID: PMC9667651 DOI: 10.1186/s12868-022-00752-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Accepted: 11/04/2022] [Indexed: 11/18/2022] Open
Abstract
Background One of the most serious nervous system diseases is spinal cord injury(SCI), which is increasing for various reasons. Although no definitive treatment has yet been identified for SCI, one possible treatment is adipose-derived stem cells(ADSCs). However, a key issue in transplantation is improving cells’ survival and function in the target tissue. Melatonin(MT) hormone with antioxidant properties can prolong cell survival and improve cell function. This study investigates the pre-conditioning of ADSCs with melatonin for enhancing the engraftment and neurological function of rats undergoing SCI. Methods 42 male Sprague–Dawley rats were divided into six groups, including Control, Sham, Model, Vehicle, and Lesion treatments A and B. After acquiring white adipose tissue, stem cells were evaluated by flow cytometry. SCI was then applied in Model, Vehicle, A, and B groups. Group A and B received ADSCs and ADSCs + melatonin, respectively, 1 week after SCI, but the vehicle received only an intravenous injection for simulation; The other groups were recruited for the behavioral test. Immunohistochemistry(IHC) was used to assess the engraftment and differentiation of ADSCs in the SCI site. Basso, Beattie, and Bresnahan's score was used to evaluate motor function between the six groups. Results Histological studies and cell count confirmed ADSCs implantation at the injury site, which was higher in the MT-ADSCs (P < 0.001). IHC revealed the differentiation of ADSCs and MT-ADSCs into neurons, astrocytes, and oligodendrocyte lineage cells, which were higher in MT-ADSCs. Functional improvement was observed in SCI + ADSCs and SCI + MT-ADSCs groups. Conclusion The pre-conditioning of ADSCs with melatonin positively affects engraftment and neuronal differentiation in SCI but does not impact performance improvement compared to the ADSCs.
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Affiliation(s)
- Arvin Naeimi
- grid.411874.f0000 0004 0571 1549Student Research Committee, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
| | - Arash Zaminy
- grid.411874.f0000 0004 0571 1549Burn and Regenerative Medicine Research Center, Velayat Hospital, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
| | - Naser Amini
- grid.411746.10000 0004 4911 7066Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Raziye Balabandi
- grid.411874.f0000 0004 0571 1549Student Research Committee, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
| | - Zoleikha Golipoor
- grid.411874.f0000 0004 0571 1549Cellular and Molecular Research Center, Faculty of Medicine, Guilan University of Medical Sciences, Rasht, Iran
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Park JH, Koh EB, Seo YJ, Oh HS, Won JY, Hwang SC, Byun JH. Tiron Has Negative Effects on Osteogenic Differentiation via Mitochondrial Dysfunction in Human Periosteum-Derived Cells. Int J Mol Sci 2022; 23:ijms232214040. [PMID: 36430519 PMCID: PMC9693013 DOI: 10.3390/ijms232214040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Revised: 11/09/2022] [Accepted: 11/13/2022] [Indexed: 11/16/2022] Open
Abstract
Tiron is a potent antioxidant that counters the pathological effects of reactive oxygen species (ROS) production due to oxidative stress in various cell types. We examined the effects of tiron on mitochondrial function and osteoblastic differentiation in human periosteum-derived cells (hPDCs). Tiron increased mitochondrial activity and decreased senescence-associated β-galactosidase activity in hPDCs; however, it had a detrimental effect on osteoblastic differentiation by reducing alkaline phosphatase (ALP) activity and alizarin red-positive mineralization, regardless of H2O2 treatment. Osteoblast-differentiating hPDCs displayed increased ROS production compared with non-differentiating hPDCs, and treatment with tiron reduced ROS production in the differentiating cells. Antioxidants decreased the rates of oxygen consumption and ATP production, which are increased in hPDCs during osteoblastic differentiation. In addition, treatment with tiron reduced the levels of most mitochondrial proteins, which are increased in hPDCs during culture in osteogenic induction medium. These results suggest that tiron exerts negative effects on the osteoblastic differentiation of hPDCs by causing mitochondrial dysfunction.
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Affiliation(s)
- Jin-Ho Park
- Department of Oral and Maxillofacial Surgery, Institute of Health Sciences, School of Medicine, Gyeongsang National University, Gyeongsang National University Hospital, Jinju 52727, Korea
- Department of Convergence Medical Science, Gyeongsang National University, Jinju 52828, Korea
| | - Eun-Byeol Koh
- Department of Oral and Maxillofacial Surgery, Institute of Health Sciences, School of Medicine, Gyeongsang National University, Gyeongsang National University Hospital, Jinju 52727, Korea
- Department of Convergence Medical Science, Gyeongsang National University, Jinju 52828, Korea
| | - Young-Jin Seo
- Department of Oral and Maxillofacial Surgery, Institute of Health Sciences, School of Medicine, Gyeongsang National University, Gyeongsang National University Hospital, Jinju 52727, Korea
- Department of Convergence Medical Science, Gyeongsang National University, Jinju 52828, Korea
| | - Hye-Seong Oh
- Department of Oral and Maxillofacial Surgery, Institute of Health Sciences, School of Medicine, Gyeongsang National University, Gyeongsang National University Hospital, Jinju 52727, Korea
- Department of Convergence Medical Science, Gyeongsang National University, Jinju 52828, Korea
| | - Ju-Yeong Won
- Department of Oral and Maxillofacial Surgery, Institute of Health Sciences, School of Medicine, Gyeongsang National University, Gyeongsang National University Hospital, Jinju 52727, Korea
- Department of Convergence Medical Science, Gyeongsang National University, Jinju 52828, Korea
| | - Sun-Chul Hwang
- Department of Orthopaedic Surgery, Institute of Health Sciences, School of Medicine, Gyeongsang National University, Jinju 52828, Korea
| | - June-Ho Byun
- Department of Oral and Maxillofacial Surgery, Institute of Health Sciences, School of Medicine, Gyeongsang National University, Gyeongsang National University Hospital, Jinju 52727, Korea
- Department of Convergence Medical Science, Gyeongsang National University, Jinju 52828, Korea
- Correspondence:
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41
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The Experimental Study of Periodontal Ligament Stem Cells Derived Exosomes with Hydrogel Accelerating Bone Regeneration on Alveolar Bone Defect. Pharmaceutics 2022; 14:pharmaceutics14102189. [PMID: 36297624 PMCID: PMC9611133 DOI: 10.3390/pharmaceutics14102189] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Revised: 10/05/2022] [Accepted: 10/09/2022] [Indexed: 12/03/2022] Open
Abstract
INTRODUCTION this study was conducted to investigate the osteogenic ability of periodontal ligament stem cells (PDLSCs) derived exosomes (PDLSCs-Exos) and the effect of PDLSCs-Exos with hydrogel on alveolar bone defect repairment in the rat. METHODS the PDLSCs were obtained through primary cell culture, and PDLSCs-Exos were purified by the ultracentrifugation method. The CCK-8 kit and ALP staining were used to explore the effect of PDLSCs-Exos on promoting the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). In vivo, the alveolar bone defect models were made mesial to the bilateral maxillary first molars of rats. MicroCT, HE staining, and Masson staining were used to analyze the new bone at the bone defect of rats. RESULTS the periodontal ligament stem cells and the periodontal ligament stem cells derived exosomes were successfully extracted. The results of the CCK-8 kit and ALP staining showed PDLSCs-Exos significantly promoted the proliferation osteogenic differentiation of BMSCs. In vivo experiment results revealed that compared with the control group and the hydrogel group, the rats in the hydrogel with exosomes group showed more new bone formation in alveolar bone defects. CONCLUSION Periodontal ligament stem cells and exosomes derived from periodontal ligament stem cells were successfully extracted. The results demonstrated that the hydrogel successfully delivered periodontal ligament stem cells derived exosomes for repairing alveolar bone defects in rats in vivo at the initial stage.
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Song WJ, Liu PP, Zheng YY, Meng ZQ, Zhu HZ, Tang CB, Li HX, Ding SJ, Zhou GH. Production of cultured fat with peanut wire-drawing protein scaffold and quality evaluation based on texture and volatile compounds analysis. Food Res Int 2022; 160:111636. [DOI: 10.1016/j.foodres.2022.111636] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2022] [Revised: 06/30/2022] [Accepted: 07/05/2022] [Indexed: 11/27/2022]
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Chen TS, Lai YA, Lai YJ, Chien CT. Adipose stem cells preincubated with theanine exert liver regeneration through increase of stem cell paracrine VEGF and suppression of ROS, pyroptosis as well as autophagy markers in liver damage induced by N-nitrosodiethylamine. Life Sci 2022; 308:120969. [PMID: 36116531 DOI: 10.1016/j.lfs.2022.120969] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Revised: 09/04/2022] [Accepted: 09/12/2022] [Indexed: 12/19/2022]
Abstract
AIMS Liver diseases induce a severe decrease in quality of life. Stem cell based therapy shows therapeutic potential in the treatment of liver injury. Theanine is a unique amino acid found in green tea and could confer beneficial effects on cell protection. This study investigates if protective effect on the liver by stem cells preincubated with theanine is better than that from stem cells without preincubated theanine. METHODS We transplanted theanine preincubated adipose-derived stem cells (ADSC) to male Wistar rats with liver dysfunction induced by N-nitrosodiethylamine. The viability, migration and antioxidant capabilities were performed in the ADSC pre-incubated with theanine. Hepatic functional, structural and molecular assays were determined in the animals with or without theanine preincubated ADSC. KEY FINDINGS Cell model revealed that ADSC preincubated with green tea theanine (T-ADSC) increased cell capabilities including viability, migration and paracrine secretion. In vivo results indicated that several pathological conditions were observed in rats with liver injury induced by DEN including structural changes and expression of pyroptosis as well as autophagy markers. The above pathological conditions were improved when the rats received both ADSC and T-ADSC treatment. Furthermore, T-ADSC showed better therapeutic effect on rats with liver injury than ADSC due to significant suppression of pyroptosis markers caspase-1 and IL-1β as well as autophagy marker LC3-II accompanied with intensive paracrine VEGF from T-ADSC. SIGNIFICANCE Increased paracrine VEGF secretion from T-ADSC plays a crucial role in liver regeneration. A future clinical study may be designed for further verification of these experimental in vivo findings.
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Affiliation(s)
- Tung-Sheng Chen
- Graduate Program of Biotechnology and Pharmaceutical Industries, National Taiwan Normal University, Taipei, Taiwan
| | - Yi-An Lai
- Department of Life Science, National Taiwan Normal University, Taipei, Taiwan
| | - Yun-Ju Lai
- Department of Life Science, National Taiwan Normal University, Taipei, Taiwan.
| | - Chiang-Ting Chien
- Department of Life Science, National Taiwan Normal University, Taipei, Taiwan.
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Jay Sarkar T, Hermsmeier M, L. Ross J, Scott Herron G. Genetic and Epigenetic Influences on Cutaneous Cellular Senescence. Physiology (Bethesda) 2022. [DOI: 10.5772/intechopen.101152] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022] Open
Abstract
Skin is the largest human organ system, and its protective function is critical to survival. The epithelial, dermal, and subcutaneous compartments are heterogeneous mixtures of cell types, yet they all display age-related skin dysfunction through the accumulation of an altered phenotypic cellular state called senescence. Cellular senescence is triggered by complex and dynamic genetic and epigenetic processes. A senescence steady state is achieved in different cell types under various and overlapping conditions of chronological age, toxic injury, oxidative stress, replicative exhaustion, DNA damage, metabolic dysfunction, and chromosomal structural changes. These inputs lead to outputs of cell-cycle withdrawal and the appearance of a senescence-associated secretory phenotype, both of which accumulate as tissue pathology observed clinically in aged skin. This review details the influence of genetic and epigenetic factors that converge on normal cutaneous cellular processes to create the senescent state, thereby dictating the response of the skin to the forces of both intrinsic and extrinsic aging. From this work, it is clear that no single biomarker or process leads to senescence, but that it is a convergence of factors resulting in an overt aging phenotype.
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Meng Z, Liu J, Feng Z, Guo S, Wang M, Wang Z, Li Z, Li H, Sui L. N-acetylcysteine regulates dental follicle stem cell osteogenesis and alveolar bone repair via ROS scavenging. Stem Cell Res Ther 2022; 13:466. [PMID: 36076278 PMCID: PMC9461171 DOI: 10.1186/s13287-022-03161-y] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2022] [Accepted: 08/28/2022] [Indexed: 12/02/2022] Open
Abstract
Background Dental follicle stem cells (DFSCs) show mesenchymal stem cell properties with the potential for alveolar bone regeneration. Stem cell properties can be impaired by reactive oxygen species (ROS), prompting us to examine the importance of scavenging ROS for stem cell-based tissue regeneration. This study aimed to investigate the effect and mechanism of N-acetylcysteine (NAC), a promising antioxidant, on the properties of DFSCs and DFSC-based alveolar bone regeneration. Methods DFSCs were cultured in media supplemented with different concentrations of NAC (0–10 mM). Cytologic experiments, RNA-sequencing and antioxidant assays were performed in vitro in human DFSCs (hDFSCs). Rat maxillary first molar extraction models were constructed, histological and radiological examinations were performed at day 7 post-surgery to investigate alveolar bone regeneration in tooth extraction sockets after local transplantation of NAC, rat DFSCs (rDFSCs) or NAC-treated rDFSCs. Results 5 mM NAC-treated hDFSCs exhibited better proliferation, less senescent rate, higher stem cell-specific marker and immune-related factor expression with the strongest osteogenic differentiation; other concentrations were also beneficial for maintaining stem cell properties. RNA-sequencing identified 803 differentially expressed genes between hDFSCs with and without 5 mM NAC. “Developmental process (GO:0032502)” was prominent, bioinformatic analysis of 394 involved genes revealed functional and pathway enrichment of ossification and PI3K/AKT pathway, respectively. Furthermore, after NAC treatment, the reduction of ROS levels (ROS, superoxide, hydrogen peroxide), the induction of antioxidant levels (glutathione, catalase, superoxide dismutase), the upregulation of PI3K/AKT signaling (PI3K-p110, PI3K-p85, AKT, phosphorylated-PI3K-p85, phosphorylated-AKT) and the rebound of ROS level upon PI3K/AKT inhibition were showed. Local transplantation of NAC, rDFSCs or NAC-treated rDFSCs was safe and promoted oral socket bone formation after tooth extraction, with application of NAC-treated rDFSCs possessing the best effect. Conclusions The proper concentration of NAC enhances DFSC properties, especially osteogenesis, via PI3K/AKT/ROS signaling, and offers clinical potential for stem cell-based alveolar bone regeneration. Supplementary Information The online version contains supplementary material available at 10.1186/s13287-022-03161-y.
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Affiliation(s)
- Zhaosong Meng
- Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Tianjin Medical University, Tianjin, China
| | - Jiacheng Liu
- Department of Prosthodontics, School and Hospital of Stomatology, Tianjin Medical University, 12 Qixiangtai Road, Tianjin, 300070, China
| | - Zhipeng Feng
- Department of Prosthodontics, School and Hospital of Stomatology, Tianjin Medical University, 12 Qixiangtai Road, Tianjin, 300070, China
| | - Shuling Guo
- Department of Prosthodontics, School and Hospital of Stomatology, Tianjin Medical University, 12 Qixiangtai Road, Tianjin, 300070, China
| | - Mingzhe Wang
- School of Stomatology, Tianjin Medical University, Tianjin, China
| | - Zheng Wang
- Department of Prosthodontics, School and Hospital of Stomatology, Tianjin Medical University, 12 Qixiangtai Road, Tianjin, 300070, China
| | - Zhe Li
- Department of Prosthodontics, School and Hospital of Stomatology, Tianjin Medical University, 12 Qixiangtai Road, Tianjin, 300070, China
| | - Hongjie Li
- School of Stomatology, Tianjin Medical University, Tianjin, China.
| | - Lei Sui
- Department of Prosthodontics, School and Hospital of Stomatology, Tianjin Medical University, 12 Qixiangtai Road, Tianjin, 300070, China.
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Huang R, Fu R, Yan Y, Liu C, Yang J, Xie Y, Li Q. Engineering hypertrophic cartilage grafts from lipoaspirate for critical-sized calvarial bone defect reconstruction: An adipose tissue-based developmental engineering approach. Bioeng Transl Med 2022; 7:e10312. [PMID: 36176620 PMCID: PMC9472001 DOI: 10.1002/btm2.10312] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2021] [Revised: 02/17/2022] [Accepted: 03/04/2022] [Indexed: 02/05/2023] Open
Abstract
Developmental engineering of living implants from different cell sources capable of stimulating bone regeneration by recapitulating endochondral ossification (ECO) is a promising strategy for large bone defect reconstruction. However, the clinical translation of these cell-based approaches is hampered by complex manufacturing procedures, poor cell differentiation potential, and limited predictive in vivo performance. We developed an adipose tissue-based developmental engineering approach to overcome these hurdles using hypertrophic cartilaginous (HyC) constructs engineered from lipoaspirate to repair large bone defects. The engineered HyC constructs were implanted into 4-mm calvarial defects in nude rats and compared with decellularized bone matrix (DBM) grafts. The DBM grafts induced neo-bone formation via the recruitment of host cells, while the HyC pellets supported bone regeneration via ECO, as evidenced by the presence of remaining cartilage analog and human NuMA-positive cells within the newly formed bone. However, the HyC pellets clearly showed superior regenerative capacity compared with that of the DBM grafts, yielding more new bone formation, higher blood vessel density, and better integration with adjacent native bone. We speculate that this effect arises from vascular endothelial growth factor and bone morphogenetic protein-2 secretion and mineral deposition in the HyC pellets before implantation, promoting increased vascularization and bone formation upon implantation. The results of this study demonstrate that adipose-derived HyC constructs can effectively heal large bone defects and present a translatable therapeutic option for bone defect repair.
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Affiliation(s)
- Ru‐Lin Huang
- Department of Plastic and Reconstructive SurgeryShanghai Ninth People's Hospital, Shanghai Jiao Tong University School of MedicineShanghaiChina
| | - Rao Fu
- Department of Plastic and Reconstructive SurgeryShanghai Ninth People's Hospital, Shanghai Jiao Tong University School of MedicineShanghaiChina
| | - Yuxin Yan
- Department of Plastic and Reconstructive SurgeryShanghai Ninth People's Hospital, Shanghai Jiao Tong University School of MedicineShanghaiChina
| | - Chuanqi Liu
- Department of Plastic and Burn SurgeryWest China Hospital, Sichuan UniversityChengduChina
| | - Jing Yang
- Department of Plastic and Reconstructive SurgeryShanghai Ninth People's Hospital, Shanghai Jiao Tong University School of MedicineShanghaiChina
| | - Yun Xie
- Department of Plastic and Reconstructive SurgeryShanghai Ninth People's Hospital, Shanghai Jiao Tong University School of MedicineShanghaiChina
| | - Qingfeng Li
- Department of Plastic and Reconstructive SurgeryShanghai Ninth People's Hospital, Shanghai Jiao Tong University School of MedicineShanghaiChina
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Yao S, Wei X, Deng W, Wang B, Cai J, Huang Y, Lai X, Qiu Y, Wang Y, Guan Y, Wang J. Nestin-dependent mitochondria-ER contacts define stem Leydig cell differentiation to attenuate male reproductive ageing. Nat Commun 2022; 13:4020. [PMID: 35821241 PMCID: PMC9276759 DOI: 10.1038/s41467-022-31755-w] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2021] [Accepted: 06/30/2022] [Indexed: 11/09/2022] Open
Abstract
Male reproductive system ageing is closely associated with deficiency in testosterone production due to loss of functional Leydig cells, which are differentiated from stem Leydig cells (SLCs). However, the relationship between SLC differentiation and ageing remains unknown. In addition, active lipid metabolism during SLC differentiation in the reproductive system requires transportation and processing of substrates among multiple organelles, e.g., mitochondria and endoplasmic reticulum (ER), highlighting the importance of interorganelle contact. Here, we show that SLC differentiation potential declines with disordered intracellular homeostasis during SLC senescence. Mechanistically, loss of the intermediate filament Nestin results in lower differentiation capacity by separating mitochondria-ER contacts (MERCs) during SLC senescence. Furthermore, pharmacological intervention by melatonin restores Nestin-dependent MERCs, reverses SLC differentiation capacity and alleviates male reproductive system ageing. These findings not only explain SLC senescence from a cytoskeleton-dependent MERCs regulation mechanism, but also suggest a promising therapy targeting SLC differentiation for age-related reproductive system diseases. The regulatory mechanisms contributing to male reproductive ageing are unknown. Here, the authors show that Nestin-dependent mito-ER contacts (MERCs) regulate stem Leydig cell (SLC) senescence and provide insights into SLCs-targeting therapies.
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Affiliation(s)
- Senyu Yao
- Scientific Research Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, 518107, China.,Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, 510080, China
| | - Xiaoyue Wei
- Scientific Research Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, 518107, China.,Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, 510080, China
| | - Wenrui Deng
- Scientific Research Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, 518107, China.,Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, 510080, China
| | - Boyan Wang
- Scientific Research Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, 518107, China.,Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, 510080, China
| | - Jianye Cai
- Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, 510080, China.,Department of Hepatic Surgery and Liver Transplantation Center of the Third Affiliated Hospital, Organ Transplantation Institute, Sun Yat-Sen University, Guangzhou, 510630, China
| | - Yinong Huang
- Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, 510080, China.,Department of Endocrinology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, China
| | - Xiaofan Lai
- Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, 510080, China.,Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China
| | - Yuan Qiu
- Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, 510080, China
| | - Yi Wang
- Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, 510080, China
| | - Yuanjun Guan
- Core Facility of Center, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, 510080, China
| | - Jiancheng Wang
- Scientific Research Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, 518107, China. .,Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, 510080, China. .,Department of Hematology, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, 518107, China.
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The Antisenescence Effect of Exosomes from Human Adipose-Derived Stem Cells on Skin Fibroblasts. BIOMED RESEARCH INTERNATIONAL 2022; 2022:1034316. [PMID: 35813225 PMCID: PMC9259368 DOI: 10.1155/2022/1034316] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Revised: 05/08/2022] [Accepted: 06/14/2022] [Indexed: 11/17/2022]
Abstract
Human adipose-derived stem cells (ADSCs) have become a promising therapeutic approach against skin aging. Recent studies confirm that exosomes partially mediate the therapeutic effect of stem cells. This study successfully isolated exosomes from the ADSC culture medium and discovered that ADSC-derived exosomes (ADSC-Exos) could alleviate human dermal fibroblast (HDF) senescence and stimulate HDF migration. Moreover, ADSC-Exos increased the type I collagen expression level and reduced the reactive oxygen species (ROS) and senescence-associated β-galactosidase (SA-β-Gal) activity in HDFs. In addition, we demonstrated that ADSC-Exos significantly inhibited senescence-related protein expression levels of p53, p21, and p16. In conclusion, our results have revealed the antisenescence effects of ADSC-Exos on HDFs and ADSC-Exos may be a novel cell-free therapeutic tool for antiaging.
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Lee SH, Won GW, Choi SH, Kim MY, Oh CH, Park JT, Park JI. Antiaging effect of inotodiol on oxidative stress in human dermal fibroblasts. Biomed Pharmacother 2022; 153:113311. [PMID: 35759867 DOI: 10.1016/j.biopha.2022.113311] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Revised: 06/06/2022] [Accepted: 06/15/2022] [Indexed: 11/24/2022] Open
Abstract
Oxidative damage is one of the major causes of human skin aging. Inotodiol is a lanostane triterpenoid that demonstrates antiviral, anticancer, and anti-inflammatory activities. Previous studies have reported that inotodiol also has antiallergic effects. However, whether inotodiol inhibits oxidative stress-induced human skin aging is not known. Stimulation of human dermal fibroblast cells with hydrogen peroxide is related to skin aging. Inotodiol inhibited the expression of mitogen-activated protein kinase (MAPK) and NADPH Oxidase 5 (NOX5). Moreover, inotodiol effectively decreased nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), as well as nitric oxide (NO), reactive oxygen species (ROS), cyclooxygenase-2 (COX-2), and cytokines such as IL-1β, IL-6, and TNF-α. Based on our results, inotodiol protects human dermal fibroblast by preventing MAPK-NOX5 and NF-κB activation and attenuates the expression of aging genes. Inotodiol may therefore be considered a potential candidate for developing natural antiaging products, because it protects the human skin from oxidative stress-induced skin aging by inhibiting the MAPK-NOX5 and NF-κB signaling pathways.
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Affiliation(s)
- Seung Hoon Lee
- Department of Biochemistry, College of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea; Translational Immunology Institute, Chungnam National University College of Medicine, Daejeon, Republic of Korea
| | - Gun-Woo Won
- Department of Biochemistry, College of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea; Brain Korea 21 FOUR Project for Medical Science, Chungnam National University, Daejeon, Republic of Korea
| | - Seung-Hyeon Choi
- Department of Biochemistry, College of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea; Translational Immunology Institute, Chungnam National University College of Medicine, Daejeon, Republic of Korea
| | - Mi-Yoon Kim
- Department of Biochemistry, College of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea
| | - Cheong-Hae Oh
- Department of Biochemistry, College of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea
| | - Jong-Tae Park
- Department of Food Science and Technology, Chungnam National University, Daejeon 34134, Republic of Korea; CARBOEXPERT Inc., Daejeon 34134, Republic of Korea.
| | - Jong-Il Park
- Department of Biochemistry, College of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea; Translational Immunology Institute, Chungnam National University College of Medicine, Daejeon, Republic of Korea; Brain Korea 21 FOUR Project for Medical Science, Chungnam National University, Daejeon, Republic of Korea.
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50
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Varesi A, Chirumbolo S, Campagnoli LIM, Pierella E, Piccini GB, Carrara A, Ricevuti G, Scassellati C, Bonvicini C, Pascale A. The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence. Antioxidants (Basel) 2022; 11:1224. [PMID: 35883714 PMCID: PMC9311946 DOI: 10.3390/antiox11071224] [Citation(s) in RCA: 60] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Revised: 06/17/2022] [Accepted: 06/21/2022] [Indexed: 02/01/2023] Open
Abstract
Cellular senescence is an irreversible state of cell cycle arrest occurring in response to stressful stimuli, such as telomere attrition, DNA damage, reactive oxygen species, and oncogenic proteins. Although beneficial and protective in several physiological processes, an excessive senescent cell burden has been involved in various pathological conditions including aging, tissue dysfunction and chronic diseases. Oxidative stress (OS) can drive senescence due to a loss of balance between pro-oxidant stimuli and antioxidant defences. Therefore, the identification and characterization of antioxidant compounds capable of preventing or counteracting the senescent phenotype is of major interest. However, despite the considerable number of studies, a comprehensive overview of the main antioxidant molecules capable of counteracting OS-induced senescence is still lacking. Here, besides a brief description of the molecular mechanisms implicated in OS-mediated aging, we review and discuss the role of enzymes, mitochondria-targeting compounds, vitamins, carotenoids, organosulfur compounds, nitrogen non-protein molecules, minerals, flavonoids, and non-flavonoids as antioxidant compounds with an anti-aging potential, therefore offering insights into innovative lifespan-extending approaches.
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Affiliation(s)
- Angelica Varesi
- Department of Biology and Biotechnology, University of Pavia, 27100 Pavia, Italy
- Almo Collegio Borromeo, 27100 Pavia, Italy
| | - Salvatore Chirumbolo
- Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, 37129 Verona, Italy;
| | | | - Elisa Pierella
- School of Medicine, Faculty of Clinical and Biomedical Sciences, University of Central Lancashire, Preston PR1 2HE, UK;
| | | | - Adelaide Carrara
- Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, Italy;
| | - Giovanni Ricevuti
- Department of Drug Sciences, University of Pavia, 27100 Pavia, Italy;
| | - Catia Scassellati
- Biological Psychiatry Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, 25123 Brescia, Italy;
| | - Cristian Bonvicini
- Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, 25123 Brescia, Italy;
| | - Alessia Pascale
- Department of Drug Sciences, Section of Pharmacology, University of Pavia, 27100 Pavia, Italy;
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