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Li X, Hayashi R, Imaizumi T, Harrington J, Kudo Y, Takayanagi H, Baba K, Nishida K. Extracellular vesicles from adipose-derived mesenchymal stem cells promote colony formation ability and EMT of corneal limbal epithelial cells. PLoS One 2025; 20:e0321579. [PMID: 40257992 PMCID: PMC12011229 DOI: 10.1371/journal.pone.0321579] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2024] [Accepted: 03/07/2025] [Indexed: 04/23/2025] Open
Abstract
Corneal diseases are a leading cause of visual impairment, and their treatment remains challenging. Corneal epithelial stem cells exist in the limbus, the peripheral region of the cornea, and play an important role in corneal regeneration. Here, we evaluated the effects of extracellular vesicles from human adipose-derived mesenchymal stem cells (AdMSC-EVs) on limbal epithelial cells (LECs). Colony formation assays showed that the colony-forming efficiency of LECs significantly increased in the presence of AdMSC-EVs. We next demonstrated that AdMSC-EVs accelerated the migration of LECs in a scratch assay, whereas the proliferation of LECs was decreased by AdMSC-EVs in the cell proliferation assay. RNA sequencing analysis of LECs indicated that AdMSC-EVs maintained their stem cell properties and improved epithelial-mesenchymal transition (EMT). Furthermore, after identifying the six most abundant microRNAs (miRNAs) in AdMSC-EVs, LEC transfection with miRNA mimics indicated that miR-25, miR-191, and miR-335 were the most probable miRNA factors within AdMSC-EVs at improving colony formation ability and EMT. Taken together, our findings indicated that AdMSC-EVs enhanced the colony formation ability and EMT of LECs, and the effects of AdMSC-EVs were in-part mediated by the miRNAs within the AdMSC-EVs.
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Affiliation(s)
- Xiaoqin Li
- Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Ryuhei Hayashi
- Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
- Department of Stem Cells and Applied Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
- Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Suita, Osaka, Japan
| | - Tsutomu Imaizumi
- Department of Stem Cells and Applied Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
- Basic Research Development Division, ROHTO Pharmaceutical, Ikuno-ku, Osaka, Japan
| | - Jodie Harrington
- Department of Stem Cells and Applied Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
- Faculty of Health, Medicine and Social Care, Medical Technology Research Centre, Anglia Ruskin University, Chelmsford Campus, England, United Kingdom
| | - Yuji Kudo
- Department of Stem Cells and Applied Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
- Basic Research Development Division, ROHTO Pharmaceutical, Ikuno-ku, Osaka, Japan
| | - Hiroshi Takayanagi
- Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
- Research, Development and Production Department of RAYMEI Inc, Suita, Osaka, Japan
| | - Koichi Baba
- Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
- Department of Advanced Device Regenerative Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
- Visual Regenerative Medicine, Division of Health Sciences, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Kohji Nishida
- Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
- Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Suita, Osaka, Japan
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Zare S, Jafarzadeh A, Zare S, Shamloo A. Exploring the dermatological applications of human mesenchymal stem cell secretome: a comprehensive review. Stem Cell Res Ther 2025; 16:177. [PMID: 40221781 PMCID: PMC11993991 DOI: 10.1186/s13287-025-04311-8] [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: 02/12/2025] [Accepted: 04/01/2025] [Indexed: 04/14/2025] Open
Abstract
INTRODUCTION Mesenchymal stem cell (MSC)-derived conditioned media is emerging as a promising alternative to stem cell therapy, owing to its abundant content of growth factors and cytokines. OBJECTIVE This review evaluates the clinical applications of MSC-conditioned media in improving scars, promoting wound healing, stimulating hair growth, and rejuvenating the skin. MATERIALS AND METHODS A thorough search of relevant databases was performed to identify studies meeting the inclusion criteria. From an initial pool of 75 articles, 16 studies published up to 2024 were selected based on their relevance, focus, and alignment with the research objectives. RESULTS Among the 17 selected studies, 5 examined the role of conditioned media in skin rejuvenation, 3 investigated its effects on hair growth, 5 assessed its efficacy in scar treatment, 2 assessed its efficacy in Inflammatory Dermatologic Disease and 2 explored its role in wound healing. All studies reported favorable outcomes, demonstrating significant improvements in scars, hair regrowth, and skin rejuvenation with the application of conditioned media. CONCLUSION This review underscores the potential of MSC-derived conditioned media in dermatology. Several studies also highlighted its enhanced therapeutic effects when combined with adjunctive treatments, such as laser therapy and microneedling, showcasing improved outcomes in dermatological care.
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Affiliation(s)
- Sona Zare
- Skin and Stem Cell Research Center, Tehran University of Medical Sciences, Tehran, Iran
- Persian Bio-Based Production (PBBP) Company, Sharif University of Technology, Tehran, Iran
- Stem Cell and Regenerative Medicine Institute, Sharif University of Technology, Azadi Street, Tarasht Avenue, Tehran, 1445613131, Iran
- Department of Mechanical Engineering, Sharif University of Technology, Tehran, Iran
| | - Alireza Jafarzadeh
- Department of Dermatology, Rasool Akram Medical Complex Clinical Research Development Center (RCRDC), School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Solmaz Zare
- Persian Bio-Based Production (PBBP) Company, Sharif University of Technology, Tehran, Iran
- Laser Application in Medical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Amir Shamloo
- Stem Cell and Regenerative Medicine Institute, Sharif University of Technology, Azadi Street, Tarasht Avenue, Tehran, 1445613131, Iran.
- Department of Mechanical Engineering, Sharif University of Technology, Tehran, Iran.
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Ma C, Zhu H, Cai Y, Li N, Han Z, Wu H, Chen H. Photobiomodulation Combined With Human Umbilical Cord Mesenchymal Stem Cells Modulates the Polarization of Microglia. JOURNAL OF BIOPHOTONICS 2025; 18:e202400468. [PMID: 39840548 DOI: 10.1002/jbio.202400468] [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: 10/22/2024] [Revised: 12/16/2024] [Accepted: 12/22/2024] [Indexed: 01/23/2025]
Abstract
Neuroinflammation plays a key role in the development of neurodegenerative diseases, with microglia regulating this process through pro-inflammatory M1 and anti-inflammatory M2 phenotypes. Studies have shown that human umbilical cord mesenchymal stem cells (hUCMSCs) modulate neuroinflammation by secreting anti-inflammatory cytokines. Photobiomodulation (PBM), a non-invasive therapy, has demonstrated significant potential in alleviating neuroinflammation. This study examines the combined effects of PBM and hUCMSCs in an in vitro microglial inflammation model and an LPS-induced mouse model. The results show that PBM-pretreated hUCMSCs promoted M2 polarization and improved cognitive function in mice by downregulating the Notch signaling pathway, suggesting a promising new approach for treating neurodegenerative diseases.
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Affiliation(s)
- Chunyan Ma
- State Key Laboratory of Separation Membranes and Membrane Processes & Key Laboratory of Hollow Fiber Membrane Materials and Membrane Processes, Tianjin Key Laboratory of Optoelectronic Detection Technology and Systems, Tiangong University, Tianjin, China
- State Key Laboratory of Advanced Medical Materials and Devices, Tianjin Key Laboratory of Neuromodulation and Neurorepair, Integrative regeneration laboratory, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
| | - Hongyu Zhu
- State Key Laboratory of Separation Membranes and Membrane Processes & Key Laboratory of Hollow Fiber Membrane Materials and Membrane Processes, Tianjin Key Laboratory of Optoelectronic Detection Technology and Systems, Tiangong University, Tianjin, China
| | - Yuanhao Cai
- State Key Laboratory of Separation Membranes and Membrane Processes & Key Laboratory of Hollow Fiber Membrane Materials and Membrane Processes, Tianjin Key Laboratory of Optoelectronic Detection Technology and Systems, Tiangong University, Tianjin, China
- School of Intelligent Information Engineering, Medicine &Technology College of Zunyi Medical University, Zunyi, China
| | - Na Li
- State Key Laboratory of Separation Membranes and Membrane Processes & Key Laboratory of Hollow Fiber Membrane Materials and Membrane Processes, Tianjin Key Laboratory of Optoelectronic Detection Technology and Systems, Tiangong University, Tianjin, China
| | - Zhibo Han
- Tianjin Key Laboratory of Engineering Technologies for Cell Pharmaceutical, National Engineering Research Center of Cell Products, AmCellGene Co. Ltd., Tianjin, China
| | - Huancheng Wu
- Department of Neurosurgery, Tianjin Beichen Hospital, Tianjin, China
| | - Hongli Chen
- State Key Laboratory of Advanced Medical Materials and Devices, Tianjin Key Laboratory of Neuromodulation and Neurorepair, Integrative regeneration laboratory, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
- Cangzhou Institute of Tiangong University, Cangzhou, China
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Yoshizumi K, Saito N, Wu Y, Shirado T, Asahi R, Mori M, Yamamoto Y, Sowa Y, Yoshimura K. Adipose-derived Stem Cells and Wound Healing Are Progressively Impaired Long-term After Radiotherapy in Mice. PLASTIC AND RECONSTRUCTIVE SURGERY-GLOBAL OPEN 2025; 13:e6419. [PMID: 39872086 PMCID: PMC11771654 DOI: 10.1097/gox.0000000000006419] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2024] [Accepted: 10/29/2024] [Indexed: 01/29/2025]
Abstract
Background The pathogenesis of deterministic radiation damage is not clearly understood, but it has been reported that fibroinflammatory pathways are up-regulated. We hypothesized that the number of adipose-derived stem/stromal cells (ASCs) decline after radiotherapies, preventing normalization of fibrosis and angiogenesis, resulting in chronic radiation damages that progress over time. Methods Dorsal skin of 8-week-old male BALB/cfC3H mice was irradiated with 10 Gy weekly for 4 weeks. At 1, 3, 6, 9, and 12 months after radiotherapy (n = 5, 5, 5, 5, and 4), tissue hemoglobin oxygen saturation, and time until epithelialization were evaluated. Skin biopsies were measured for thickness and CD34+/isolectin- stem/stromal cell count. Nonirradiated (NRT) controls were evaluated at each time point as well (n = 5 each). Results Compared with NRT controls, time until epithelialization was significantly longer at 1 month (28 ± 3, P < 0.01); not statistically different at 3 months (16 ± 2, P = 0.32); and lengthened over time at 6 months (20 ± 2, P = 0.21), 9 months (28 ± 2, P < 0.01), and 12 months (26 ± 3, P < 0.01), as did tissue oxygen saturation. The number of CD34+/isolectin- ASCs decreased over time, at 1 month (5.3 ± 1.3, P = 0.01), 3 months (6.0 ± 1.4, P = 0.03), 6 months (4.0 ± 0.8, P < 0.01), 9 months (1.7 ± 0.5, P < 0.01), and 12 months (0.3 ± 0.5, P < 0.01). The subcutaneous fatty layer was significantly thinner at 3 months (116 ± 33, P < 0.01), 6 months (147 ± 22, P = 0.02), 9 months (52 ± 12, P = 0.04), and 12 months (89 ± 19, P = 0.04), but not at 1 month (141 ± 18, P = 0.43). Conclusions After 6 months postirradiation, the number of ASCs continued to decline over time, accompanied by irreversible progression of fibrosis, atrophy, and ischemia, which resulted in impaired wound healing.
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Affiliation(s)
- Kayo Yoshizumi
- From the Department of Plastic Surgery, Jichi Medical University, Tochigi, Japan
| | - Natsumi Saito
- From the Department of Plastic Surgery, Jichi Medical University, Tochigi, Japan
| | - Yunyan Wu
- From the Department of Plastic Surgery, Jichi Medical University, Tochigi, Japan
| | - Takako Shirado
- From the Department of Plastic Surgery, Jichi Medical University, Tochigi, Japan
| | - Rintaro Asahi
- From the Department of Plastic Surgery, Jichi Medical University, Tochigi, Japan
| | - Masanori Mori
- From the Department of Plastic Surgery, Jichi Medical University, Tochigi, Japan
| | - Yoshihiro Yamamoto
- From the Department of Plastic Surgery, Jichi Medical University, Tochigi, Japan
| | - Yoshihiro Sowa
- From the Department of Plastic Surgery, Jichi Medical University, Tochigi, Japan
| | - Kotaro Yoshimura
- From the Department of Plastic Surgery, Jichi Medical University, Tochigi, Japan
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Zangiabadi I, Ilaghi M, Shamsara A, Eftekhar‐Vaghefi SH, Saheli M, Shabani M. Exploring the impact of acetylsalicylic acid and conditioned medium obtained from mesenchymal cells, individually and in combination, on cognitive function, histological changes, and oxidant-antioxidant balance in male rats with hippocampal injury. Brain Behav 2024; 14:e70010. [PMID: 39262160 PMCID: PMC11391022 DOI: 10.1002/brb3.70010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2024] [Revised: 07/16/2024] [Accepted: 08/03/2024] [Indexed: 09/13/2024] Open
Abstract
BACKGROUND The hippocampus is susceptible to damage, leading to negative impacts on cognition. Conditioned medium (CM) obtained from adipose tissue-derived mesenchymal stem cells (MSCs) and acetylsalicylic acid (ASA) have shown neuroprotective effects independently. This study explored the synergistic potential of ASA and CM from adipose-derived MSCs against hippocampal injury. METHODS Adult male Wistar rats received bilateral hippocampal ethidium bromide (EB) injections to induce hippocampal damage. Rats were treated with ASA and/or CM derived from adipose tissue MSCs every 48 h for 16 days. Behavioral tests (open field test, Morris water maze, novel object recognition, and passive avoidance), oxidative stress, Western blot analysis of brain-derived neurotrophic factor (BDNF) and cerebral dopamine neurotrophic factor (CDNF) expression, and hippocampal histological investigation were conducted. RESULTS Administration of EB caused impairments in spatial, recognition, and passive avoidance memory, as well as heightened oxidative stress, reduced BDNF/CDNF expression, and pyramidal cell loss in the hippocampal CA1 region. Administration of ASA, CM, or a combination of both mitigated these hippocampal damages and cognitive deficits, elevated BDNF and CDNF levels, and alleviated the CA1 necrosis caused by EB. Moreover, co-administering ASA and CM resulted in greater improvements in spatial memory compared to administering ASA alone, suggesting possible synergistic interactions. CONCLUSIONS The ability of ASA, CM obtained from adipose tissue-derived MSCs, and their combination therapy to alleviate hippocampal injuries highlights their promising therapeutic potential as a neuroprotection strategy against brain damage. Our findings provide preliminary evidence of the potential synergistic effects of ASA and CM, which warrants further investigations.
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Affiliation(s)
- Iman Zangiabadi
- Department of Anatomy, Afzalipour School of MedicineKerman University of Medical SciencesKermanIran
| | - Mehran Ilaghi
- Institute of Neuropharmacology, Kerman Neuroscience Research CenterKerman University of Medical SciencesKermanIran
| | - Ali Shamsara
- Department of Anatomy, Afzalipour School of MedicineKerman University of Medical SciencesKermanIran
- Institute of Neuropharmacology, Kerman Neuroscience Research CenterKerman University of Medical SciencesKermanIran
| | | | - Mona Saheli
- Department of Anatomy, Afzalipour School of MedicineKerman University of Medical SciencesKermanIran
| | - Mohammad Shabani
- Institute of Neuropharmacology, Kerman Neuroscience Research CenterKerman University of Medical SciencesKermanIran
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Kim DY, Ko E, Ryu YH, Lee SJ, Jun YJ. Hyaluronic Acid Based Adipose Tissue-Derived Extracellular Matrix Scaffold in Wound Healing: Histological and Immunohistochemical Study. Tissue Eng Regen Med 2024; 21:829-842. [PMID: 38647955 PMCID: PMC11286915 DOI: 10.1007/s13770-024-00644-2] [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: 01/10/2024] [Revised: 03/13/2024] [Accepted: 03/20/2024] [Indexed: 04/25/2024] Open
Abstract
BACKGROUND In this study, we explored the potential of human adipose tissue-derived extracellular matrix (adECM) sheets augmented with crosslinked hyaluronic acid (HA) as advanced wound dressings. We aimed to enhance healing efficacy while optimizing cost efficiency. METHODS The adECM was processed from healthy donor tissue and combined with crosslinked HA to form ECM-HA sheets (Scaffiller, Medikan, Korea). In vitro experiments involved seeding adipose-derived stem cells (ASCs) onto these sheets and assessing cell survival and cytokine production. In vivo testing utilized a rat wound model, comparing ECM-HA sheet with HA-based dressing and polyurethane foam dressing. Re-epithelialization and collagen deposition were examined through histopathological examinations, whereas immunohistochemistry was used to assess CD31, alpha smooth muscle actin (α-SMA), and Tenascin C expression as contributing factors to wound healing. RESULTS Results indicated that ECM-HA sheets were produced efficiently, with enhanced growth factor production and ASC survival observed in vitro. In vivo, ECM-HA sheets demonstrated accelerated wound healing, evidenced by improved epithelialization, thicker dermis, increased collagen deposition, and enhanced vascularity. Notably, they exhibited reduced myofibroblast activity and increased expression of Tenascin C, suggesting a favorable healing environment. CONCLUSION ECM-HA sheets offer a promising approach for wound management, combining the benefits of adECM and HA. They present improved stability and cost-effectiveness while promoting essential aspects of wound healing such as angiogenesis and collagen formation. This study underscores the therapeutic potential of ECM-HA sheets in clinical applications aimed at facilitating wound repair.
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Affiliation(s)
- Dong Yeon Kim
- Department of Plastic and Reconstructive Surgery, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Eunjeong Ko
- Department of Plastic and Reconstructive Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-Gu, Seoul, 137-701, Republic of Korea
| | - Yeon Hee Ryu
- Department of Plastic and Reconstructive Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-Gu, Seoul, 137-701, Republic of Korea
| | - Su Jin Lee
- Department of Plastic and Reconstructive Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-Gu, Seoul, 137-701, Republic of Korea
| | - Young Joon Jun
- Department of Plastic and Reconstructive Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-Gu, Seoul, 137-701, Republic of Korea.
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Lin Z, Lin D, Lin D. The Mechanisms of Adipose Stem Cell-Derived Exosomes Promote Wound Healing and Regeneration. Aesthetic Plast Surg 2024; 48:2730-2737. [PMID: 38438760 DOI: 10.1007/s00266-024-03871-z] [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: 08/11/2023] [Accepted: 01/25/2024] [Indexed: 03/06/2024]
Abstract
Chronic wound healing is a class of diseases influenced by multiple complex factors, causing severe psychological and physiological impact on patients. It is an intractable clinical challenge and its possible mechanisms are not yet clear. It has been proven that adipose stem cell-derived exosomes (ADSC-Exos) can promote wound healing and inhibit scar formation by regulating inflammation, promoting cell proliferation, migration, and angiogenesis, regulating matrix remodeling, which provides a new approach for wound healing through biological treatment. This review focuses on the mechanism, treatment, and administration methods of ADSC-Exos in wound healing, providing a comprehensive understanding the mechanisms of ADSC-Exos on wound healing. LEVEL OF EVIDENCE I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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Affiliation(s)
- Zhengjie Lin
- Department of Metabolism and Endocrinology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China
| | - Danyi Lin
- Department of Pathology, Guangdong Provincial People's Hospital, Southern Medical University, Guangzhou, China.
| | - Dane Lin
- Neonatal Intensive Care Unit, Department of Pediatrics, The First Affiliated Hospital of Shantou University Medical College, No. 57 Changping Road, Shantou, Guangdong, China.
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Wang M, Zhao J, Li J, Meng M, Zhu M. Insights into the role of adipose-derived stem cells and secretome: potential biology and clinical applications in hypertrophic scarring. Stem Cell Res Ther 2024; 15:137. [PMID: 38735979 PMCID: PMC11089711 DOI: 10.1186/s13287-024-03749-6] [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: 03/03/2024] [Accepted: 05/01/2024] [Indexed: 05/14/2024] Open
Abstract
Scar tissue is the inevitable result of repairing human skin after it has been subjected to external destructive stimuli. It leads to localized damage to the appearance of the skin, accompanied by symptoms such as itching and pain, which reduces the quality of life of the patient and causes serious medical burdens. With the continuous development of economy and society, there is an increasing demand for beauty. People are looking forward to a safer and more effective method to eliminate pathological scarring. In recent years, adipose-derived stem cells (ADSCs) have received increasing attention from researchers. It can effectively improve pathological scarring by mediating inflammation, regulating fibroblast proliferation and activation, and vascular reconstruction. This review focuses on the pathophysiological mechanisms of hypertrophic scarring, summarizing the therapeutic effects of in vitro, in vivo, and clinical studies on the therapeutic effects of ADSCs in the field of hypertrophic scarring prevention and treatment, the latest application techniques, such as cell-free therapies utilizing ADSCs, and discussing the advantages and limitations of ADSCs. Through this review, we hope to further understand the characterization of ADSC and clarify the effectiveness of its application in hypertrophic scarring treatment, so as to provide clinical guidance.
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Affiliation(s)
- Menglin Wang
- Department of Plastic Surgery, The First Affiliated Hospital, Dalian Medical University, No. 222, Zhongshan Road, Xigang District, Dalian, 116011, China
| | - Jianyu Zhao
- Department of Orthopaedics, The First Affiliated Hospital, Dalian Medical University, No. 222, Zhongshan Road, Xigang District, Dalian, 116011, China
| | - Jiacheng Li
- Department of Plastic Surgery, The Second Affiliated Hospital, Dalian Medical University, Dalian, China
| | - Meng Meng
- Department of Orthopaedics, The First Affiliated Hospital, Dalian Medical University, No. 222, Zhongshan Road, Xigang District, Dalian, 116011, China.
| | - Mengru Zhu
- Department of Plastic Surgery, The First Affiliated Hospital, Dalian Medical University, No. 222, Zhongshan Road, Xigang District, Dalian, 116011, China.
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Enosawa S, Kobayashi S, Kobayashi E. Proposal of Simplified Standardization of the Cell-Growth-Promoting Activity of Human Adipose Tissue Mesenchymal Stromal Cell Culture Supernatants. Int J Mol Sci 2024; 25:5197. [PMID: 38791236 PMCID: PMC11121723 DOI: 10.3390/ijms25105197] [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: 04/03/2024] [Revised: 04/27/2024] [Accepted: 05/07/2024] [Indexed: 05/26/2024] Open
Abstract
The conditioned medium (CM) obtained from mesenchymal stromal cell (MSC) culture has excellent cell growth-promoting activity and is used for cosmetics and healthcare products. Unlike pharmaceuticals, strict efficacy verification is not legally required for these products. However, their efficacy must be substantiated as commercial products. We attempted to simplify CM production and to standardize the evaluation of the growth-promoting activity of CM. CM was obtained through the culturing of two lines of commercially available human adipose tissue-derived MSCs using MEMα with or without 10% fetal bovine serum (FBS) for 24 h. Non-CM control media were produced by the same protocol without MSCs. Growth-promoting activities of the CM were estimated by [3H]-thymidine pulse. CM were subjected to molecular weight fractionation with ultrafiltration using 10 k-, 30 k-, 50 k-, and 100 k-membranes. The FBS-free CMs showed 1.34- to 1.85-fold increases and FBS-containing CMs showed 1.45- to 1.67-fold increases in proliferation-promoting activity compared with non-CM controls, regardless of the source of the cell. The thymidine incorporation levels were approximately three times higher in FBS-containing CMs. Aged cells also showed 1.67- to 2.48-fold increases in the activity due to FBS-containing CM, but not to FBS-free CM. The CM activities were sustained even after 1 year at 4 °C. Molecular weight fractionation showed that the activity was recovered in the fraction above 100 k. Clear and stable cell-growth-promoting activity was confirmed with CMs of commercially available adipose tissue MSCs. The activity was detected in the fraction over 100 k. We propose here the importance of standardizing the production and evaluation of CMs to indicate their specific action.
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Affiliation(s)
- Shin Enosawa
- Center for Regenerative Medicine, National Center for Child Health and Development, Tokyo 157-8535, Japan;
- Kobayashi Regenerative Research Institute, LLC, Wakayama 640-8263, Japan
| | - Sho Kobayashi
- Kobayashi Regenerative Research Institute, LLC, Wakayama 640-8263, Japan
| | - Eiji Kobayashi
- Kobayashi Regenerative Research Institute, LLC, Wakayama 640-8263, Japan
- Department of Kidney Regenerative Medicine, The Jikei University School of Medicine, Tokyo 105-8461, Japan
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Sohrabi K, Ahmadi H, Amini A, Ahrabi B, Mostafavinia A, Omidi H, Mirzaei M, Fadaei Fathabady F, Fridoni M, Rahmannia M, Chien S, Bayat M. Promising improvement in infected Wound Healing in Type two Diabetic rats by Combined effects of conditioned medium of human adipose-derived stem cells plus Photobiomodulation. Lab Anim Res 2023; 39:29. [PMID: 37964303 PMCID: PMC10648630 DOI: 10.1186/s42826-023-00178-z] [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: 07/21/2023] [Revised: 10/23/2023] [Accepted: 10/27/2023] [Indexed: 11/16/2023] Open
Abstract
BACKGROUND We aimed to examine the accompanying and solo impacts of conditioned medium of human adipose-derived stem cells (h-ASC-COM) and photobiomodulation (PBM) on the maturation stage of an ischemic infected delayed-healing wound model (IIDHWM) of rats with type 2 diabetes (TIIDM). RESULTS Outcomes of the wound closure ratio (WCR) results, tensiometrical microbiological, and stereological assessment followed almost identical patterns. While the outcomes of h-ASC-COM + PBM, PBM only, and h-ASC-COM only regimes were significantly better for all evaluated methods than those of group 1(all, p < 0.001), PBM alone and h-ASC-COM + PBM therapy achieved superior results than h-ASC-COM only (ranged from p = 0.05 to p < 0.001). In terms of tensiometrical and stereological examinations, the results of h-ASC-COM + PBM experienced better results than the PBM only (all, p < 0.001). CONCLUSIONS h-ASC-COM + PBM, PBM, and h-ASC-COM cures expressively accelerated the maturation stage in the wound healing process of IIDHWM with MRSA in TIIDM rats by diminishing the inflammatory reaction, and the microbial flora of MRSA; and increasing wound strength, WCR, number of fibroblasts, and new blood vessels. While the h-ASC-COM + PBM and PBM were more suitable than the effect of h-ASC-COM, the results of h-ASC-COM + PBM were superior to PBM only.
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Affiliation(s)
- Kaysan Sohrabi
- School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Houssein Ahmadi
- Department of Biology and Anatomical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Abdollah Amini
- Department of Biology and Anatomical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Behnaz Ahrabi
- Department of Biology and Anatomical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Atarodalsadat Mostafavinia
- Department of Anatomical Sciences and Cognitive Neuroscience, School of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Hamidreza Omidi
- Department of Biology and Anatomical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mansooreh Mirzaei
- Department of Anatomy, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
| | - Fatemeh Fadaei Fathabady
- Department of Biology and Anatomical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammadjavad Fridoni
- Department of Biology and Anatomical Sciences, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Maryam Rahmannia
- School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sufan Chien
- Price Institute of Surgical Research, University of Louisville and Noveratech LLC, Louisville, KY, USA
| | - Mohammad Bayat
- Price Institute of Surgical Research, University of Louisville and Noveratech LLC, Louisville, KY, USA.
- Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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11
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Humenik F, Danko J, Krešáková L, Vdoviaková K, Vrabec V, Vasilová E, Giretová M, Tóth Š, Fagová Z, Babík J, Medvecký Ľ. A Chitosan-Based Biomaterial Combined with Mesenchymal Stem Cell-Conditioned Medium for Wound Healing and Skin Regeneration. Int J Mol Sci 2023; 24:16080. [PMID: 38003269 PMCID: PMC10671656 DOI: 10.3390/ijms242216080] [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: 10/11/2023] [Revised: 11/03/2023] [Accepted: 11/06/2023] [Indexed: 11/26/2023] Open
Abstract
The aim of this study was to provide a beneficial treatment effect of novel chitosan bio-polymeric material enriched with mesenchymal stem cell products derived from the canine adipose tissue (AT-MSC) on the artificial skin defect in a rabbit model. For the objectivity of the regeneration evaluation, we used histological analysis and a scoring system created by us, taking into account all the attributes of regeneration, such as inflammatory reaction, necrosis, granulation, formation of individual skin layers and hair follicles. We observed an acceleration and improvement in the healing of an artificially created skin defect after eight and ten weeks in comparison with negative control (spontaneous healing without biomaterial). Moreover, we were able to described hair follicles and epidermis layer in histological skin samples treated with a chitosan-based biomaterial on the eighth week after grafting.
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Affiliation(s)
- Filip Humenik
- Department of Morphological Sciences, University of Veterinary Medicine and Pharmacy in Košice, 041 81 Košice, Slovakia
| | - Ján Danko
- Department of Morphological Sciences, University of Veterinary Medicine and Pharmacy in Košice, 041 81 Košice, Slovakia
- Educational, Scientific and Research Institute AGEL, 811 06 Bratislava, Slovakia
| | - Lenka Krešáková
- Department of Morphological Sciences, University of Veterinary Medicine and Pharmacy in Košice, 041 81 Košice, Slovakia
| | - Katarína Vdoviaková
- Department of Morphological Sciences, University of Veterinary Medicine and Pharmacy in Košice, 041 81 Košice, Slovakia
| | - Vladimír Vrabec
- Clinic of Birds, Exotic and Free Living Animals, University of Veterinary Medicine and Pharmacy in Košice, 041 81 Košice, Slovakia
| | - Emília Vasilová
- Clinic of Birds, Exotic and Free Living Animals, University of Veterinary Medicine and Pharmacy in Košice, 041 81 Košice, Slovakia
| | - Mária Giretová
- Division of Functional and Hybrid Systems, Institute of Materials Research of SAS, 040 01 Košice, Slovakia
| | - Štefan Tóth
- Department of Histology and Embryology, University of Pavol Jozef Šafárik, 041 80 Košice, Slovakia
| | - Zuzana Fagová
- Department of Histology and Embryology, University of Pavol Jozef Šafárik, 041 80 Košice, Slovakia
| | - Ján Babík
- Clinic of Burns and Reconstructive Medicine, AGEL Hospital, 040 15 Košice-Šaca, Slovakia
| | - Ľubomír Medvecký
- Department of Morphological Sciences, University of Veterinary Medicine and Pharmacy in Košice, 041 81 Košice, Slovakia
- Division of Functional and Hybrid Systems, Institute of Materials Research of SAS, 040 01 Košice, Slovakia
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12
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Liu YX, Sun JM, Ho CK, Gao Y, Wen DS, Liu YD, Huang L, Zhang YF. Advancements in adipose-derived stem cell therapy for skin fibrosis. World J Stem Cells 2023; 15:342-353. [PMID: 37342214 PMCID: PMC10277960 DOI: 10.4252/wjsc.v15.i5.342] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Revised: 03/30/2023] [Accepted: 04/13/2023] [Indexed: 05/26/2023] Open
Abstract
Pathological scarring and scleroderma, which are the most common conditions of skin fibrosis, pathologically manifest as fibroblast proliferation and extracellular matrix (ECM) hyperplasia. Fibroblast proliferation and ECM hyperplasia lead to fibrotic tissue remodeling, causing an exaggerated and prolonged wound-healing response. The pathogenesis of these diseases has not been fully clarified and is unfortunately accompanied by exceptionally high medical needs and poor treatment effects. Currently, a promising and relatively low-cost treatment has emerged-adipose-derived stem cell (ASC) therapy as a branch of stem cell therapy, including ASCs and their derivatives-purified ASC, stromal vascular fraction, ASC-conditioned medium, ASC exosomes, etc., which are rich in sources and easy to obtain. ASCs have been widely used in therapeutic settings for patients, primarily for the defection of soft tissues, such as breast enhancement and facial contouring. In the field of skin regeneration, ASC therapy has become a hot research topic because it is beneficial for reversing skin fibrosis. The ability of ASCs to control profibrotic factors as well as anti-inflammatory and immunomodulatory actions will be discussed in this review, as well as their new applications in the treatment of skin fibrosis. Although the long-term effect of ASC therapy is still unclear, ASCs have emerged as one of the most promising systemic antifibrotic therapies under development.
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Affiliation(s)
- Yu-Xin Liu
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, Shanghai 200011, China
| | - Jia-Ming Sun
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, Shanghai 200011, China
| | - Chia-Kang Ho
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, Shanghai 200011, China
| | - Ya Gao
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, Shanghai 200011, China
| | - Dong-Sheng Wen
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, Shanghai 200011, China
| | - Yang-Dan Liu
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, Shanghai 200011, China
| | - Lu Huang
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, Shanghai 200011, China
| | - Yi-Fan Zhang
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, Shanghai 200011, China
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Cell-Free Therapies: The Use of Cell Extracts to Mitigate Irradiation-Injured Salivary Glands. BIOLOGY 2023; 12:biology12020305. [PMID: 36829582 PMCID: PMC9953449 DOI: 10.3390/biology12020305] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Revised: 02/06/2023] [Accepted: 02/07/2023] [Indexed: 02/17/2023]
Abstract
Radiotherapy is a standard treatment for head and neck cancer patients worldwide. However, millions of patients who received radiotherapy consequently suffer from xerostomia because of irreversible damage to salivary glands (SGs) caused by irradiation (IR). Current treatments for IR-induced SG hypofunction only provide temporary symptom alleviation but do not repair the damaged SG, thus resulting in limited treatment efficacy. Therefore, there has recently been a growing interest in regenerative treatments, such as cell-free therapies. This review aims to summarize cell-free therapies for IR-induced SG, with a particular emphasis on utilizing diverse cell extract (CE) administrations. Cell extract is a group of heterogeneous mixtures containing multifunctional inter-cellular molecules. This review discusses the current knowledge of CE's components and efficacy. We propose optimal approaches to improve cell extract treatment from multiple perspectives (e.g., delivery routes, preparation methods, and other details regarding CE administration). In addition, the advantages and limitations of CE treatment are systematically discussed by comparing it to other cell-free (such as conditioned media and exosomes) and cell-based therapies. Although a comprehensive identification of the bioactive factors within CEs and their mechanisms of action have yet to be fully understood, we propose cell extract therapy as an effective, practical, user-friendly, and safe option to conventional therapies in IR-induced SG.
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14
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Li S, Sun J, Yang J, Yang Y, Ding H, Yu B, Ma K, Chen M. Gelatin methacryloyl (GelMA) loaded with concentrated hypoxic pretreated adipose-derived mesenchymal stem cells(ADSCs) conditioned medium promotes wound healing and vascular regeneration in aged skin. Biomater Res 2023; 27:11. [PMID: 36782342 PMCID: PMC9926638 DOI: 10.1186/s40824-023-00352-3] [Citation(s) in RCA: 49] [Impact Index Per Article: 24.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2022] [Accepted: 02/04/2023] [Indexed: 02/15/2023] Open
Abstract
BACKGROUND Aging skin is characterized by a disturbed structure and lack of blood supply, which makes it difficult to heal once injured. ADSCs secrete large amounts of cytokines, which promote wound healing and vascular regeneration through paracrine secretion, and the number of cytokines can be elevated by hypoxic pretreating. However, the components of ADSCs are difficult to retain in wounds. Gelatin methacrylate (GelMA) is a photopolymerizable hydrogel synthesized from gelatin and has recently emerged as a potentially attractive material for tissue engineering applications. GelMA loaded with concentrated hypoxic pretreated ADSCs conditioned medium could provide a new method of treating wounds in aged skin. METHODS Primary ADSCs were isolated from human adipose tissue and characterized by flow cytometry and differentiation test. ADSCs in passages 4-6 were pretreated in the hypoxic and normoxic environments to collect conditioned medium, the conditioned medium was then concentrated to prepare concentrated ADSCs conditioned medium(cADSC-CM)(the one collected from ADSCs under hypoxia was called hypo-CM ,and the one from normoxia was called nor-CM). The concentration of cytokines was detected. After treated with cADSC-CM, the abilities of proliferation, migration, and tube formation of human umbilical vascular endothelial cells (HUVECs) were assayed, and Akt/mTOR and MAPK signal pathway was detected using western blotting. GelMA+hypo-CM hydrogel was prepared, and a comprehensive evaluation of morphology, protein release efficiency, degradation rate, mechanical properties, and rheology properties were performed. Full-thickness skin wounds were created on the backs of 20-month-old mice. After surgery, GelMA, GelMA+F12, GelMA+hypo-CM, and GelMA+nor-CM were applied to the wound surface respectively. H&E, Masson, and immunohistochemistry staining were performed, and a laser Doppler perfusion imager was used to evaluate the blood perfusion. The student's t-test was used for analysis between two groups and a one-way analysis of variance (ANOVA) was used for analysis among multi groups. RESULTS Our results revealed that 1) wounds in aged skin healed more slowly than that in young skin and exhibited poorer perfusion; 2) hypoxic pretreated ADSCs secreted more cytokines including VEGF by activating HIF1α; 3) hypo-CM promoted proliferation and migration of HUVECs through VEGF/Akt/mTOR and MAPK signal pathway; 4) GelMA-hypoCM accelerated wound healing and angiogenesis in aged skin in vivo. CONCLUSION GelMA loaded with concentrated hypoxic pretreated adipose-derived mesenchymal stem cells conditioned medium could accelerate wound healing in aged skin by promoting angiogenesis.
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Affiliation(s)
- Shiyi Li
- grid.414252.40000 0004 1761 8894Senior Department of Burns and Plastic Surgery, The Fourth Medical Center of Chinese PLA General Hospital, No. 51 Fucheng Road, Haidian District, Beijing, 100038 China ,grid.488137.10000 0001 2267 2324Chinese PLA Medical School, Beijing, 100853 China
| | - Jiachen Sun
- grid.414252.40000 0004 1761 8894Senior Department of Burns and Plastic Surgery, The Fourth Medical Center of Chinese PLA General Hospital, No. 51 Fucheng Road, Haidian District, Beijing, 100038 China ,grid.411472.50000 0004 1764 1621Department of Dermatology and Venerology, Peking University First Hospital, Beijing, 100034 China
| | - Jinxiu Yang
- grid.414252.40000 0004 1761 8894Senior Department of Burns and Plastic Surgery, The Fourth Medical Center of Chinese PLA General Hospital, No. 51 Fucheng Road, Haidian District, Beijing, 100038 China ,grid.506261.60000 0001 0706 78397th Department of Plastic Surgery, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100144 China
| | - Yi Yang
- grid.414252.40000 0004 1761 8894Senior Department of Burns and Plastic Surgery, The Fourth Medical Center of Chinese PLA General Hospital, No. 51 Fucheng Road, Haidian District, Beijing, 100038 China ,grid.488137.10000 0001 2267 2324Chinese PLA Medical School, Beijing, 100853 China
| | - Hongfan Ding
- grid.414252.40000 0004 1761 8894Senior Department of Burns and Plastic Surgery, The Fourth Medical Center of Chinese PLA General Hospital, No. 51 Fucheng Road, Haidian District, Beijing, 100038 China ,grid.488137.10000 0001 2267 2324Chinese PLA Medical School, Beijing, 100853 China
| | - Boya Yu
- grid.414252.40000 0004 1761 8894Senior Department of Burns and Plastic Surgery, The Fourth Medical Center of Chinese PLA General Hospital, No. 51 Fucheng Road, Haidian District, Beijing, 100038 China ,grid.488137.10000 0001 2267 2324Chinese PLA Medical School, Beijing, 100853 China
| | - Kui Ma
- grid.414252.40000 0004 1761 8894Research Center for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Division, Chinese PLA General Hospital, Beijing, 100048 China
| | - Minliang Chen
- Senior Department of Burns and Plastic Surgery, The Fourth Medical Center of Chinese PLA General Hospital, No. 51 Fucheng Road, Haidian District, Beijing, 100038, China.
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15
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Silveira BM, Ribeiro TO, Freitas RS, Carreira ACO, Gonçalves MS, Sogayar M, Meyer R, Birbrair A, Fortuna V. Secretome from human adipose-derived mesenchymal stem cells promotes blood vessel formation and pericyte coverage in experimental skin repair. PLoS One 2022; 17:e0277863. [PMID: 36534643 PMCID: PMC9762598 DOI: 10.1371/journal.pone.0277863] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Accepted: 11/04/2022] [Indexed: 12/24/2022] Open
Abstract
Human adipose tissue-derived stem cells (hASC) secretome display various therapeutically relevant effects in regenerative medicine, such as induction of angiogenesis and tissue repair. The benefits of hASC secretome are primarily orchestrated by trophic factors that mediate autocrine and paracrine effects in host cells. However, the composition and the innate characteristics of hASC secretome can be highly variable depending on the culture conditions. Here, we evaluated the combined effect of serum-free media and hypoxia preconditioning on the hASCs secretome composition and biological effects on angiogenesis and wound healing. The hASCs were cultured in serum-free media under normoxic (NCM) or hypoxic (HCM) preconditioning. The proteomic profile showed that pro- and anti-antiangiogenic factors were detected in NCM and HCM secretomes. In vitro studies demonstrated that hASCs secretomes enhanced endothelial proliferation, survival, migration, in vitro tube formation, and in vivo Matrigel plug angiogenesis. In a full-thickness skin-wound mouse model, injection of either NCM or HCM significantly accelerated the wound healing. Finally, hASC secretomes were potent in increasing endothelial density and vascular coverage of resident pericytes expressing NG2 and nestin to the lesion site, potentially contributing to blood vessel maturation. Overall, our data suggest that serum-free media or hypoxic preconditioning enhances the vascular regenerative effects of hASC secretome in a preclinical wound healing model.
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Affiliation(s)
- Brysa M. Silveira
- Health Science Institute, Federal University of Bahia, Salvador, BA, Brazil
| | - Tiago O. Ribeiro
- Health Science Institute, Federal University of Bahia, Salvador, BA, Brazil
| | - Railane S. Freitas
- Health Science Institute, Federal University of Bahia, Salvador, BA, Brazil
| | - Ana C. O. Carreira
- Department of Surgery, School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil
| | - Marilda Souza Gonçalves
- Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, BA, Brazil
- Department of Clinical Analysis, Faculty of Pharmacy, Federal University of Bahia, Salvador, BA, Brazil
| | - Mari Sogayar
- Cell and Molecular Therapy Center (NUCEL), Medical School, University of São Paulo, São Paulo, Brazil
- Biochemistry Department, Chemistry Institute, University of São Paulo, São Paulo, SP, Brazil
| | - Roberto Meyer
- Health Science Institute, Federal University of Bahia, Salvador, BA, Brazil
| | - Alexander Birbrair
- Department of Pathology, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil
- Department of Radiology, Columbia University Medical Center, New York, NY, United States of America
- Department of Dermatology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, United States of America
| | - Vitor Fortuna
- Health Science Institute, Federal University of Bahia, Salvador, BA, Brazil
- Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, BA, Brazil
- * E-mail:
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Zhang Y, Zhang M, Yao A, Xie Y, Lin J, Sharifullah F, Hong Y, Chen H, Cheng F, Lai W. Circ_0011129 Encapsulated by the Small Extracellular Vesicles Derived from Human Stem Cells Ameliorate Skin Photoaging. Int J Mol Sci 2022; 23:ijms232315390. [PMID: 36499715 PMCID: PMC9739284 DOI: 10.3390/ijms232315390] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Revised: 10/31/2022] [Accepted: 11/02/2022] [Indexed: 12/12/2022] Open
Abstract
Photoaging is not only the main cause of skin aging caused by exogenous factors, it is also related to a variety of skin diseases and even malignant tumors. Excessive and repeated exposure to ultraviolet radiation, especially UVA induces oxidative stress, DNA damage, inflammation, and collagen and elastin degeneration, ultimately leads to skin photoaging, manifested by skin redness, coarse wrinkles, and pigmentation even skin cancer. There has been a large demand of effective prevention and medications but approaches in the current management of photoaging are very limited. In the previous study, we found that a non-coding circular RNA circ_0011129 acts as a miR-6732-5p adsorption sponge to inhibit the reduction of type I collagen and the denaturation and accumulation of elastin in UVA-induced HDF cells photoaging model. However, in vivo instability and efficient delivery to the target cell of circRNA is a major challenge for its clinical application. Therefore, improving its stability and delivery efficiency are desired. In this study, we proposed a strategy of delivering circ_0011129 with small extracellular vesicles (sEVs) from human adipose-derived stem cells (hADSCs) to intervene in the photoaging process. The results showed that sEVs from hADSCs in 3D bioreactor culture (3D-sEVs) can prevent photoaging. Consequently, by overexpressing circ_0011129 in hADSCs, we successfully loaded it into 3D-sEVs (3D-circ-sEVs) and its protective effect was better. Our studies provide a novel approach to preventing skin photoaging, which has important clinical significance and application value for the development of non-coding RNA drugs to treat skin photoaging. We first screened out hADSCs-derived sEVs with excellent anti-oxidant effects. We then compared the sEVs collected from traditional 2D culture with 3D bioreactor culture. By miRNA-seq and GEO data analysis, we found that miRNAs in 3D-sEVs were enriched in cell activities related to apoptosis, cellular senescence, and inflammation. Subsequently, we prepared circ_0011129-loaded 3D-sEVs (3D-circ-sEVs) by overexpressing it in hADSCs for the treatment of photoaging in vitro. We proved that 3D-circ-sEVs can interfere with the process of cell photoaging and protect cells from UVA radiation damage, as well as in a H2O2-induced oxidative stress model.
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Affiliation(s)
- Yu Zhang
- Department of Dermato-Venereology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510000, China
| | - Manqi Zhang
- School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen 518107, China
| | - Amin Yao
- Department of Dermato-Venereology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510000, China
| | - Yalin Xie
- Department of Dermato-Venereology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510000, China
| | - Jingxiong Lin
- School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen 518107, China
| | - Farooqi Sharifullah
- Department of Plastic Surgery, Sun Yat-sen University, Guangzhou 510000, China
| | - Yixin Hong
- Department of Dermato-Venereology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510000, China
| | - Hongbo Chen
- School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen 518107, China
| | - Fang Cheng
- School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen 518107, China
- Correspondence: (W.L.); (F.C.)
| | - Wei Lai
- Department of Dermato-Venereology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510000, China
- Correspondence: (W.L.); (F.C.)
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17
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Wang X, Ma Y, Niu X, Su T, Huang X, Lu F, Chang Q. Direct three-dimensional printed egg white hydrogel wound dressing promotes wound healing with hitching adipose stem cells. Front Bioeng Biotechnol 2022; 10:930551. [PMID: 36072289 PMCID: PMC9441893 DOI: 10.3389/fbioe.2022.930551] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Accepted: 07/25/2022] [Indexed: 11/13/2022] Open
Abstract
Current wound dressing based on hydrogel offers a promising way to accelerate the healing process, yet great challenges remain in the development of a highly integrated and efficient platform with the combination of therapeutic biomolecules and stem cells. Herein, a natural hydrogel wound dressing from egg white can be conveniently obtained by feasible physical crosslinking, the prepared hydrogel dressing features interconnected microporous channels, direct 3D printing, cytocompatibility, and intrinsic biomolecules to advance cell behavior. The 3D printed egg white hydrogels promote the adhesion and proliferation of adipose-derived stem cells (ASCs) without obvious cytotoxicity. In addition, this integrated hydrogel platform accompanied with adipose-derived stem cells accelerates wound healing through the enhancement of fibroblast proliferation, angiogenesis, and collagen rearrangement in the wound bed. The egg white hydrogel provides an effective wound caring product possessing low cost, easy availability along with ready manufacturing, and advanced therapeutic effect, which may be extended for the management of chronic or other complicated wounds.
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Affiliation(s)
| | | | | | | | | | - Feng Lu
- *Correspondence: Feng Lu, ; Qiang Chang,
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Guo X, Schaudinn C, Blume-Peytavi U, Vogt A, Rancan F. Effects of Adipose-Derived Stem Cells and Their Conditioned Medium in a Human Ex Vivo Wound Model. Cells 2022; 11:cells11071198. [PMID: 35406762 PMCID: PMC8998073 DOI: 10.3390/cells11071198] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Revised: 03/23/2022] [Accepted: 03/30/2022] [Indexed: 12/14/2022] Open
Abstract
Adult stem cells have been extensively investigated for tissue repair therapies. Adipose-derived stem cells (ASCs) were shown to improve wound healing by promoting re-epithelialization and vascularization as well as modulating the inflammatory immune response. In this study, we used ex vivo human skin cultured in a six-well plate with trans-well inserts as a model for superficial wounds. Standardized wounds were created and treated with allogeneic ASCs, ASCs conditioned medium (ASC-CM), or cell culture medium (DMEM) supplemented with fetal calf serum (FCS). Skin viability (XTT test), histology (hematoxylin and eosin, H and E), β-catenin expression as well as inflammatory mediators and growth factors were monitored over 12 days of skin culture. We observed only a moderate time-dependent decrease in skin metabolic activity while skin morphology was preserved, and re-epithelialization occurred at the wound edges. An increase in β-catenin expression was observed in the newly formed epithelia, especially in the samples treated with ASC-CM. In general, increased growth factors and inflammatory mediators, e.g., hepatocytes growth factor (HGF), platelet-derived growth factor subunit AA (PDGF-AA), IL-1α, IL-7, TNF-α, and IL-10, were observed over the incubation time. Interestingly, different expression profiles were observed for the different treatments. Samples treated with ASC-CM significantly increased the levels of inflammatory cytokines and PDGF-AA with respect to control, whereas the treatment with ASCs in DMEM with 10% FCS resulted in significantly increased levels of fibroblast growth factor-basic (FGF-basic) and moderate increases of immunomodulatory cytokines. These results confirm that the wound microenvironment can influence the type of mediators secreted by ASCs and the mode as to how they improve the wound healing process. Comparative investigations with pre-activated ASCs will elucidate further aspects of the wound healing mechanism and improve the protocols of ACS application.
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Affiliation(s)
- Xiao Guo
- Clinical Research Center for Hair and Skin Science, Department of Dermatology, Venerology and and Allergy, Charité–Universitaetsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany; (X.G.); (U.B.-P.); (A.V.)
| | - Christoph Schaudinn
- Advanced Light and Electron Microscopy, Zentrum für Biologische Gefahren und Spezielle Pathogene 4 (ZBS4), Robert Koch Institute, 13353 Berlin, Germany;
| | - Ulrike Blume-Peytavi
- Clinical Research Center for Hair and Skin Science, Department of Dermatology, Venerology and and Allergy, Charité–Universitaetsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany; (X.G.); (U.B.-P.); (A.V.)
| | - Annika Vogt
- Clinical Research Center for Hair and Skin Science, Department of Dermatology, Venerology and and Allergy, Charité–Universitaetsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany; (X.G.); (U.B.-P.); (A.V.)
| | - Fiorenza Rancan
- Clinical Research Center for Hair and Skin Science, Department of Dermatology, Venerology and and Allergy, Charité–Universitaetsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany; (X.G.); (U.B.-P.); (A.V.)
- Correspondence: ; Tel.: +49-30-450518347
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19
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Zhang S, Zhang Y, Min P. Single-Cell and Bulk Transcriptome Data Integration Reveals Dysfunctional Cell Types and Aberrantly Expressed Genes in Hypertrophic Scar. Front Genet 2022; 12:806740. [PMID: 35047019 PMCID: PMC8762316 DOI: 10.3389/fgene.2021.806740] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Accepted: 12/09/2021] [Indexed: 12/11/2022] Open
Abstract
Hypertrophic scar (HS) is a common skin disorder characterized by excessive extracellular matrix (ECM) deposition. However, it is still unclear how the cellular composition, cell-cell communications, and crucial transcriptionally regulatory network were changed in HS. In the present study, we found that FB-1, which was identified a major type of fibroblast and had the characteristics of myofibroblast, was significantly expanded in HS by integrative analysis of the single-cell and bulk RNA sequencing (RNA-seq) data. Moreover, the proportion of KC-2, which might be a differentiated type of keratinocyte (KC), was reduced in HS. To decipher the intercellular signaling, we conducted the cell-cell communication analysis between the cell types, and found the autocrine signaling of HB-1 through COL1A1/2-CD44 and CD99-CD99 and the intercellular contacts between FB-1/FB-5 and KC-2 through COL1A1/COL1A2/COL6A1/COL6A2-SDC4. Almost all the ligands and receptors involved in the autocrine signaling of HB-1 were upregulated in HS by both scRNA-seq and bulk RNA-seq data. In contrast, the receptor of KC-2, SDC4, which could bind to multiple ligands, was downregulated in HS, suggesting that the reduced proportion of KC-2 and apoptotic phenotype of KC-2 might be associated with the downregulation of SDC4. Furthermore, we also investigated the transcriptionally regulatory network involved in HS formation. The integrative analysis of the scRNA-seq and bulk RNA-seq data identified CREB3L1 and TWIST2 as the critical TFs involved in the myofibroblast of HS. In summary, the integrative analysis of the single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data greatly improved our understanding of the biological characteristics during the HS formation.
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Affiliation(s)
- Shunuo Zhang
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yixin Zhang
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Peiru Min
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
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