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Hoseini SM, Moghimi F, Hosseini ES, Miresmaeili SM, Mehrjardi MYV, Dehghani M, Sheikhha MH, Montazeri F. Microenvironment-Dependent MSC Immunoregulation in Type 1 Diabetes: Insights From IFNγ Preconditioning. Genes Cells 2025; 30:e70032. [PMID: 40491292 DOI: 10.1111/gtc.70032] [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: 09/07/2024] [Revised: 05/25/2025] [Accepted: 05/28/2025] [Indexed: 06/11/2025]
Abstract
Interferon-gamma (IFNγ) plays a crucial role in the pathogenesis of type 1 diabetes (T1D) and is widely utilized to license mesenchymal stem/stromal cells (MSCs) to enhance their immunosuppressive properties through a process known as preconditioning or priming. This study investigates the interaction of MSCs preconditioned with (IFNγ+) or without (IFNγ-) IFNγ, with peripheral blood mononuclear cells (PBMCs) from healthy controls (HC) and T1D patients. We assessed the effects of these interactions on anti-inflammatory gene expression, chemokine and receptor profiles, and the induction of regulatory T (Treg) cells. Our findings reveal contrasting responses in HC and T1D PBMCs when exposed to IFNγ+ and IFNγ- MSCs, particularly in the expression of key genes such as CXCR3 and its ligands (CXCL9, CXCL10), CXCR6, CCR5, and its ligands (CCL3 and CCL4). Pathway enrichment analysis further showed that IFNγ preconditioning tailors MSC responses to specific immune microenvironments. These differential gene expression patterns were also reflected in the proportions of Treg cells, which varied depending on whether paracrine signaling or direct cell contact was involved. Collectively, our results demonstrate that IFNγ+ and IFNγ- MSCs create distinct immunomodulatory microenvironments in T1D PBMCs compared to HC PBMCs, emphasizing the potential for tailored MSC-based therapies in T1D treatment.
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Affiliation(s)
- Seyed Mehdi Hoseini
- Biotechnology Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
- Hematology and Oncology Research Center, Non-Communicable Diseases Research Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | | | - Elham Sadat Hosseini
- Biotechnology Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | | | | | - Mohammadreza Dehghani
- Abortion Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Mohammad Hasan Sheikhha
- Biotechnology Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Fateme Montazeri
- Abortion Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
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Han D, Liu W, Gong J, Ma Y, Sun Z. Challenges and future perspectives in using mesenchymal stem cells for efficient bone fracture healing. Front Bioeng Biotechnol 2025; 13:1568914. [PMID: 40521093 PMCID: PMC12162511 DOI: 10.3389/fbioe.2025.1568914] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2025] [Accepted: 05/08/2025] [Indexed: 06/18/2025] Open
Abstract
Mesenchymal stem cells (MSCs) demonstrate considerable potential for enhancing bone fracture healing due to their multipotency and immunomodulatory properties. This review investigates the relationship between MSCs, the immune system, and the skeletal microenvironment, focusing on the roles of cytokines and signaling pathways in osteogenesis. The healing process of bone fractures is complex and involves a coordinated response from various cell types, including immune cells and MSCs, which secrete bioactive molecules that promote tissue regeneration and modulate inflammation. Despite their promise, challenges such as variability in MSC sources, ethical considerations, regulatory restrictions, and obstacles in achieving effective delivery and retention at fracture sites restrict their clinical application. Recent advancements in MSC-based therapies, including innovative biomaterials, three-dimensional bioprinting, and gene editing technologies, aim to improve the therapeutic efficacy of MSCs. In addition, strategies to rejuvenate aged MSCs and enhance their regenerative capabilities are critical for addressing age-related fractures, as the functionality of MSCs declines with age. Understanding the mechanisms underlying MSC action, including their paracrine signaling and interaction with the bone microenvironment, is essential for optimizing their therapeutic use. Addressing existing limitations in MSC research and application provides a comprehensive perspective on the future of MSC therapies in bone repair. This review discusses the transformative potential of MSCs in regenerative medicine and orthopedics, highlighting the need for further research to unlock their full capabilities and improve clinical outcomes in patients with bone injuries.
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Affiliation(s)
| | | | | | | | - Zhengwen Sun
- Yantaishan Hospital, Trauma Orthopedics, Yantai, China
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3
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Goff AD, Zhang X, Thomas B, Ong SSY, Atala A, Zhang Y. Body Fluid-Derived Stem Cells: Powering Innovative, Less-Invasive Cell Therapies. Int J Mol Sci 2025; 26:4382. [PMID: 40362618 PMCID: PMC12072510 DOI: 10.3390/ijms26094382] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2025] [Revised: 05/02/2025] [Accepted: 05/02/2025] [Indexed: 05/15/2025] Open
Abstract
Stem cell therapy offers significant promise for tissue regeneration and repair. Traditionally, bone marrow- and adipose-derived stem cells have served as primary sources, but their clinical use is limited by invasiveness and low cell yield. This review focuses on body fluid-derived stem cells as an emerging, non-invasive, and readily accessible alternative. We examine stem cells isolated from amniotic fluid, peripheral blood, cord blood, menstrual fluid, urine, synovial fluid, breast milk, and cerebrospinal fluid, highlighting their unique biological properties and therapeutic potential. By comparing their characteristics and barriers to clinical translation, we propose body fluid-derived stem cells as a promising source for regenerative applications, with continued research needed to fully achieve their clinical utility.
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Affiliation(s)
- Adam David Goff
- Wake Forest Institute for Regenerative Medicine, School of Medicine, Wake Forest University, Winston-Salem, NC 27101, USA; (A.D.G.); (X.Z.)
- School of Medicine, Wake Forest University, Winston-Salem, NC 27101, USA
| | - Xinyue Zhang
- Wake Forest Institute for Regenerative Medicine, School of Medicine, Wake Forest University, Winston-Salem, NC 27101, USA; (A.D.G.); (X.Z.)
| | - Biju Thomas
- Keck School of Medicine of USC, University of Southern California, Los Angeles, CA 90033, USA
| | - Sally Shin Yee Ong
- Department of Ophthalmology, School of Medicine, Wake Forest University, Winston-Salem, NC 27101, USA
| | - Anthony Atala
- Wake Forest Institute for Regenerative Medicine, School of Medicine, Wake Forest University, Winston-Salem, NC 27101, USA; (A.D.G.); (X.Z.)
| | - Yuanyuan Zhang
- Wake Forest Institute for Regenerative Medicine, School of Medicine, Wake Forest University, Winston-Salem, NC 27101, USA; (A.D.G.); (X.Z.)
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Hoseini SM, Montazeri F. The influence of cell source on the senescence of human mesenchymal stem/stromal cells. Hum Cell 2025; 38:87. [PMID: 40221541 DOI: 10.1007/s13577-025-01213-y] [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: 10/24/2024] [Accepted: 03/28/2025] [Indexed: 04/14/2025]
Abstract
While mesenchymal stem/stromal cells (MSCs) exhibit the ability to self-renew, they are not immortal; they eventually reach a point of irreversible growth cessation and functional deterioration following a limited series of population doublings, referred to as replicative senescence. When evaluated according to the criteria set by the International Society for Cell Therapy (ISCT), MSCs show significant differences in their senescence patterns and other characteristics related to their phenotype and function. These differences are attributed to the source of the MSCs and the conditions in which they are grown. MSCs derived from fetal or adult sources have variations in their genome stability, as well as in the expression and epigenetic profile of the cells, which in turn affects their secretome. Understanding the key factors of MSC senescence based on cell source can help to develop effective strategies for regulating senescence and improving the therapeutic potential.
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Affiliation(s)
- Seyed Mehdi Hoseini
- Biotechnology Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
- Hematology and Oncology Research Center, Non-communicable Diseases Research Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Fateme Montazeri
- Abortion Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, No. 1. Safaeyeh. Bou-Al Ave., Yazd, 8916877391, Iran.
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Tao Q, Wu Y, Pang H, Lv P, Li W, Nie X, Han FY. Effect of administration routes on the efficacy of human umbilical cord mesenchymal stem cells in type 2 diabetic rats. Front Endocrinol (Lausanne) 2025; 16:1536655. [PMID: 40190404 PMCID: PMC11968364 DOI: 10.3389/fendo.2025.1536655] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2024] [Accepted: 03/03/2025] [Indexed: 04/09/2025] Open
Abstract
Background Human umbilical cord mesenchymal stem cells (UCMSCs) are being investigated in various clinical trials for different conditions, including type 2 diabetes mellitus (T2DM). However, there is limited research on the optimal injection routes for UCMSCs in T2DM, particularly intravenous injection. Objective The objective of this study aims to investigate the efficacy of four different administration routes of UCMSCs in treating T2DM rats, including pancreas injection (DP), tail vein injection (DT), intraperitoneal injection (DI), and dorsal pancreatic artery injection (DPA). Results After two weeks of UCMSCs treatment, the fasting blood glucose levels in the DT group decreased significantly. The oral glucose tolerance test (OGTT) levels and the islet structure in the DT group almost recovered to normal. The contents of C-P and GLP-1 in serum increased significantly in all treatment groups, while the levels of INS, TNF-α, IL-6, IL-1β, IAA, and GSP decreased significantly. These improvements were further observed after four weeks of UCMSCs treatment. Histological analysis confirmed the progression of pancreatic recovery in all treatment groups, with the DT group showing the most significant improvement, correlating with the observed efficacy. Immunohistochemistry results further demonstrated increased insulin and PDX-1 expression, along with reduced glucagon levels in UCMSCs-treated rats. Additionally, liver and kidney function significantly improved across all treatment groups, with the DT group showing the best outcomes. Conclusion Overall, these findings suggest that the administration route significantly affected the efficacy of UCMSCs in treating T2DM, with tail vein injection showing the most effective results.
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Affiliation(s)
- Qiqiang Tao
- Hainan Beautech Stem Cell Anti-Aging Hospital, Qionghai, Hainan, China
| | - Youzhi Wu
- Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD, Australia
| | - Huiwen Pang
- Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD, Australia
| | - Pinglei Lv
- Hainan Beautech Stem Cell Anti-Aging Hospital, Qionghai, Hainan, China
| | - Wenrui Li
- Hainan Beautech Stem Cell Anti-Aging Hospital, Qionghai, Hainan, China
| | - Xuqiang Nie
- Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD, Australia
- College of Pharmacy, Zunyi Medical University, Zunyi, China
- Key Lab of the Basic Pharmacology of the Ministry of Education & Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, China
| | - Felicity Y. Han
- Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD, Australia
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Liu S, Wang T, Liu Y, Li Y, Ma J, Hu Q, Wang H, Zhang X. Human placental mesenchymal stem cells ameliorates premature ovarian insufficiency via modulating gut microbiota and suppressing the inflammation in rats. PLoS One 2025; 20:e0313763. [PMID: 40043087 PMCID: PMC11882084 DOI: 10.1371/journal.pone.0313763] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Accepted: 10/31/2024] [Indexed: 05/13/2025] Open
Abstract
The core objective of this study was to explore the effects and potential mechanism of human placental mesenchymal stem cells (PMSCs) in improving early-onset ovarian dysfunction (POI). Mesenchymal stem cells with multidirectional differentiation ability were isolated from human placenta tissue and a culture system of human PMSCs was constructed for this study. Subsequently, we successfully constructed POI rat models using cisplatin induction. We randomly divided these models into four groups: CON group (blank control), MOD group (POI model), MED group (hormone therapy), and PMSC group (PMSCs therapy). Then, we compared the differences in estrus cycle, ovarian index, ovarian weight, and ovarian histopathological features, as well as hormones and inflammatory factors in rats of diverse groups. The content of lipopolysaccharide (LPS) in plasma was determined by limulus reagent kit. 16S rDNA sequencing was used to evaluate the changes in gut flora composition. Further, we investigated short-chain fatty acids (SCFAs) in the metabolites of rat gut microbiota by gas chromatography-mass spectrometry (GC-MS). As a result, we successfully established an efficient cell culture system of human placental mesenchymal stem cells (PMSCs) in vitro. Then, we evaluated the effects of PMSC intervention on POI rats: Compared to the untreated MOD group, the estrous cycle of rats in the PMSC group gradually became regular, the ovarian weight and ovarian index were significantly increased, and the ovarian tissue structure was improved by showing an increase in the number of follicles and a decrease in the number of atretic follicles. Moreover, PMSC intervention significantly affected plasma sex hormones by a major impact on follicle stimulating hormone (FSH) and Estradiol (E2). In terms of inflammatory factors, PMSC intervention decreased the levels of proinflammatory cytokines including interleukin (IL)-1β, IL-33, IL-6, and tumor necrosis factor (TNF)-α in plasma and ovarian tissue of POI rats. Meanwhile, the expression of anti-inflammatory cytokine IL-10 was increased. In addition, we found that there was ectopic lipopolysaccharide (LPS) in the blood of POI rats, which could be significantly reduced by PMSC intervention. Intestinal microbiota sequencing and analysis showed that after PMSC intervention, the phyla abundances of Firmicutes, Bacteroides, and Proteobacteria showed remarkable differences between the MOD and PMSC groups (P < 0.05). Further genus analysis showed that PMSC treatment had a major influence in gut microbitoa by increasing the abundances of Turicibacter and Desulfovibrio, as well as reducing Alloprevotella, Parabacteroides, Rikenellaceae_RC9_gut_group, and Rikenella. The changes of SCFAs in intestinal microbial metabolites of rats after PMSC intervention were analyzed: caproic acid level was markedly increased, butyric acid showed a decreased trend. Notably, we found a closed and complicated potential correlation among differential microbiota, inflammatory factors and hormones after PMSCs intervention. Collectively, this study have successfully established a suitable cultured PMSCs that can effectively promote the improvement of reproductive function in POI rats and achieve therapeutic effects by regulating the inflammatory response and reshaping the gut intestinal microbiota.
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Affiliation(s)
- Shudan Liu
- School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, Ningxia, China
- Ningxia Medical University General Hospital, Yinchuan, Ningxia, China
| | - Ting Wang
- School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, Ningxia, China
| | - Yuanyuan Liu
- School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, Ningxia, China
| | - Yiwei Li
- School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, Ningxia, China
| | - Junbai Ma
- School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, Ningxia, China
| | - Qikuan Hu
- School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, Ningxia, China
| | - Hao Wang
- School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, Ningxia, China
| | - Xiaoxia Zhang
- College of Traditional Chinese Medicine, Ningxia Medical University, Yinchuan, Ningxia, China
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Li L, He Y, Zhao J, Yin H, Feng X, Fan X, Wu W, Lu Q. Mesenchymal Stromal Cell-Based Therapy: A Promising Approach for Autoimmune Diseases. Clin Rev Allergy Immunol 2025; 68:21. [PMID: 39982546 DOI: 10.1007/s12016-025-09030-9] [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] [Accepted: 02/04/2025] [Indexed: 02/22/2025]
Abstract
Autoimmune diseases are characterized by immune dysregulation, resulting in aberrant reactivity of T cells and antibodies to self-antigens, leading to various patterns of inflammation and organ dysfunction. However, current therapeutic agents exhibit broad-spectrum activity and lack disease-specific selectivity, leading to enduring adverse effects, notably severe infections, and malignancies, and patients often fail to achieve the intended clinical goals. Mesenchymal stromal cells (MSCs) are multipotent stromal cells that can be easily derived from various tissues, such as adipose tissue, umbilical cords, Wharton's jelly, placenta, and dental tissues. MSCs offer advantages due to their immunomodulatory and anti-inflammatory abilities, low immunogenicity, and a high capacity for proliferation and multipotent differentiation, making them excellent candidates for cell-based treatment in autoimmune disorders. This review will cover preclinical studies and clinical trials involving MSCs in autoimmune diseases, as well as the primary challenges associated with the clinical application of MSC therapies and strategies for maximizing their therapeutic potential.
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Affiliation(s)
- Liming Li
- Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China
- Key Laboratory of Basic and Translational Research On Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Nanjing, China
| | - Yong He
- Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China
| | - Junpeng Zhao
- Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China
- Key Laboratory of Basic and Translational Research On Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Nanjing, China
- Department of Clinical Laboratory, Xiangya Hospital, Central South University, Changsha, China
| | - Huiqi Yin
- Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China
- Key Laboratory of Basic and Translational Research On Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Nanjing, China
| | - Xiwei Feng
- Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China
- Key Laboratory of Basic and Translational Research On Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Nanjing, China
| | - Xinyu Fan
- Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China
- Key Laboratory of Basic and Translational Research On Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Nanjing, China
| | - Wei Wu
- Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China
- Key Laboratory of Basic and Translational Research On Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Nanjing, China
| | - Qianjin Lu
- Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China.
- Key Laboratory of Basic and Translational Research On Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Nanjing, China.
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Duan Y, Chen X, Shao H, Li Y, Zhang Z, Li H, Zhao C, Xiao H, Wang J, Zhang X. Enhanced immunosuppressive capability of mesenchymal stem cell-derived small extracellular vesicles with high expression of CD73 in experimental autoimmune uveitis. Stem Cell Res Ther 2024; 15:149. [PMID: 38783393 PMCID: PMC11118760 DOI: 10.1186/s13287-024-03764-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2024] [Accepted: 05/20/2024] [Indexed: 05/25/2024] Open
Abstract
BACKGROUND Autoimmune uveitis is an inflammatory disease triggered by an aberrant immune response. Mesenchymal stem cell-derived small extracellular vesicles (MSC-sEVs) are emerging as potential therapeutic agents for this condition. CD73, an ectoenzyme present on MSC-sEVs, is involved in mitigating inflammation by converting extracellular adenosine monophosphate into adenosine. We hypothesize that the inhibitory effect of MSC-sEVs on experimental autoimmune uveitis (EAU) could be partially attributed to the surface expression of CD73. METHODS To investigate novel therapeutic approaches for autoimmune uveitis, we performed lentiviral transduction to overexpress CD73 on the surface of MSC-sEVs, yielding CD73-enriched MSC-sEVs (sEVs-CD73). Mice with interphotoreceptor retinoid-binding protein (IRBP)-induced EAU were grouped randomly and treated with 50 µg MSC-sEVs, vector infected MSC-sEVs, sEVs-CD73 or PBS via single tail vein injection. We evaluated the clinical and histological features of the induced mice and analyzed the proportion and functional capabilities of T helper cells. Furthermore, T-cells were co-cultured with various MSC-sEVs in vitro, and we quantified the resulting inflammatory response to assess the potential therapeutic benefits of sEVs-CD73. RESULTS Compared to MSC-sEVs, sEVs-CD73 significantly alleviates EAU, leading to reduced inflammation and diminished tissue damage. Treatment with sEVs-CD73 results in a decreased proportion of Th1 cells in the spleen, draining lymph nodes, and eyes, accompanied by an increased proportion of regulatory T-cells (Treg cells). In vitro assays further reveal that sEVs-CD73 inhibits T-cell proliferation, suppresses Th1 cells differentiation, and enhances Treg cells proportion. CONCLUSION Over-expression of CD73 on MSC-sEVs enhances their immunosuppressive effects in EAU, indicating that sEVs-CD73 has the potential as an efficient immunotherapeutic agent for autoimmune uveitis.
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Affiliation(s)
- Yanan Duan
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China
| | - Xiteng Chen
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China
| | - Hui Shao
- Department of Ophthalmology and Visual Sciences, Kentucky Lions Eye Center, School of Medicine, University of Louisville, Louisville, KY, USA
| | - Yongtao Li
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China
| | - Zhihui Zhang
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China
| | - Huan Li
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China
| | - Chuan Zhao
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China
| | - Hong Xiao
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China
| | - Jiawei Wang
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China
| | - Xiaomin Zhang
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China.
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Ni J, Ye D, Zeng W, Ma S, Wang Z, Kuang Y, Yang L. Promotion of hair growth by a conditioned medium from human umbilical cord mesenchymal stem cells cultivated in a 3D scaffold of gelatin sponge. Eur J Med Res 2024; 29:270. [PMID: 38704575 PMCID: PMC11069168 DOI: 10.1186/s40001-024-01830-7] [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: 12/18/2023] [Accepted: 04/05/2024] [Indexed: 05/06/2024] Open
Abstract
BACKGROUND This study aims to investigate the effects of a conditioned medium (CM) from human umbilical cord mesenchymal stem cells (HuMSCs) cultivated in gelatin sponge (GS-HuMSCs-CM) on hair growth in a mouse model. METHODS CM was collected from the HuMSCs cultivated in a monolayer or in a gelatin sponge. Vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF-1), keratinocyte growth factor (KGF), and hepatocyte growth factor (HGF) levels in CMs were measured by enzyme-linked immunosorbent assays (ELISAs). A hair loss model by a C57 BL/6J mouse was prepared. The effects of GS-HuMSCs-CM and HuMSCs on hair regrowth in mice were investigated by intradermal injection in the depilated back skin with normal saline (NS) as the control. The time for hair regrowth and full covering in depilated areas was observed, and the hair growth was evaluated histologically and by grossly measuring hair length and diameter. RESULTS Compared with monolayer cultured cells, the three-dimensional (3D) culture of HuMSCs in gelatin sponge drastically increased VEGF, IGF-1, KGF, and HGF production. GS-HuMSCs-CM and HuMSCs injection both promoted hair regeneration in mice, while GS-HuMSCs-CM presented more enhanced effects in hair length, hair diameter, and growth rate. GS-HuMSCs-CM significantly promoted angiogenesis in injected skin areas, which might also contribute to faster hair regrowth. CONCLUSION GS-HuMSCs-CM exerted significant effects on inducing hair growth and promoted skin angiogenesis in C57BL/6J mice.
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Affiliation(s)
- Jintao Ni
- Department of Plastic Surgery and Burns Center, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China
| | - Danyan Ye
- Research Center for Translational Medicine, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China
| | - Weiping Zeng
- Department of Plastic Surgery and Burns Center, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China
| | - Siyi Ma
- Department of Plastic Surgery and Burns Center, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China
| | - Zhixia Wang
- Department of Plastic Surgery and Burns Center, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China
| | - Yuping Kuang
- Department of Plastic Surgery and Burns Center, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China
| | - Lujun Yang
- Department of Plastic Surgery and Burns Center, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China.
- Research Center for Translational Medicine, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China.
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10
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Maraldi T, Russo V. Amniotic Fluid and Placental Membranes as Sources of Stem Cells: Progress and Challenges 2.0. Int J Mol Sci 2023; 24:16020. [PMID: 38003210 PMCID: PMC10671515 DOI: 10.3390/ijms242216020] [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: 10/31/2023] [Accepted: 11/06/2023] [Indexed: 11/26/2023] Open
Abstract
The aim of the second edition of this Special Issue was to collect both review and original research articles that investigate and elucidate the possible therapeutic role of perinatal stem cells in pathological conditions, such as cardiovascular and metabolic diseases, as well as inflammatory, autoimmune, musculoskeletal, and degenerative diseases [...].
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Affiliation(s)
- Tullia Maraldi
- Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Via del Pozzo 71, 41125 Modena, Italy
| | - Valentina Russo
- Faculty of Bioscience and Agro-Food and Environmental Technology, Agriculture and Environment, University of Teramo, Via Renato Balzarini 1, 64100 Teramo, Italy
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11
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Rosner M, Horer S, Feichtinger M, Hengstschläger M. Multipotent fetal stem cells in reproductive biology research. Stem Cell Res Ther 2023; 14:157. [PMID: 37287077 DOI: 10.1186/s13287-023-03379-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2023] [Accepted: 05/16/2023] [Indexed: 06/09/2023] Open
Abstract
Due to the limited accessibility of the in vivo situation, the scarcity of the human tissue, legal constraints, and ethical considerations, the underlying molecular mechanisms of disorders, such as preeclampsia, the pathological consequences of fetomaternal microchimerism, or infertility, are still not fully understood. And although substantial progress has already been made, the therapeutic strategies for reproductive system diseases are still facing limitations. In the recent years, it became more and more evident that stem cells are powerful tools for basic research in human reproduction and stem cell-based approaches moved into the center of endeavors to establish new clinical concepts. Multipotent fetal stem cells derived from the amniotic fluid, amniotic membrane, chorion leave, Wharton´s jelly, or placenta came to the fore because they are easy to acquire, are not associated with ethical concerns or covered by strict legal restrictions, and can be banked for autologous utilization later in life. Compared to adult stem cells, they exhibit a significantly higher differentiation potential and are much easier to propagate in vitro. Compared to pluripotent stem cells, they harbor less mutations, are not tumorigenic, and exhibit low immunogenicity. Studies on multipotent fetal stem cells can be invaluable to gain knowledge on the development of dysfunctional fetal cell types, to characterize the fetal stem cells migrating into the body of a pregnant woman in the context of fetomaternal microchimerism, and to obtain a more comprehensive picture of germ cell development in the course of in vitro differentiation experiments. The in vivo transplantation of fetal stem cells or their paracrine factors can mediate therapeutic effects in preeclampsia and can restore reproductive organ functions. Together with the use of fetal stem cell-derived gametes, such strategies could once help individuals, who do not develop functional gametes, to conceive genetically related children. Although there is still a long way to go, these developments regarding the usage of multipotent fetal stem cells in the clinic should continuously be accompanied by a wide and detailed ethical discussion.
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Affiliation(s)
- Margit Rosner
- Institute of Medical Genetics, Center for Pathobiochemistry and Genetics, Medical University of Vienna, Währinger Strasse 10, 1090, Vienna, Austria
| | - Stefanie Horer
- Institute of Medical Genetics, Center for Pathobiochemistry and Genetics, Medical University of Vienna, Währinger Strasse 10, 1090, Vienna, Austria
| | | | - Markus Hengstschläger
- Institute of Medical Genetics, Center for Pathobiochemistry and Genetics, Medical University of Vienna, Währinger Strasse 10, 1090, Vienna, Austria.
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12
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Jamshidi V, Halabian R, Saeedi P, Bagheri H, Nobakht Motlagh Ghoochani BF. Accelerating synergistic effects of preconditioned mesenchymal stem cells with Crocin and dexamethasone in pulmonary epithelial cells injury. Toxicol Res (Camb) 2023; 12:369-380. [PMID: 37397913 PMCID: PMC10311171 DOI: 10.1093/toxres/tfad016] [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: 12/10/2022] [Revised: 02/14/2023] [Accepted: 03/19/2023] [Indexed: 07/04/2023] Open
Abstract
Chemical warfare victims suffer from bronchiolitis and chronic pulmonary obstruction caused by sulfur mustard (SM) toxicity. Despite the mesenchymal stem cells capacity to alleviate inflammation, their low survival rate under oxidative stress severely limits their effectiveness. This study aimed to examine how natural (Crocin) and synthetic (Dexamethasone) antioxidants might affect MSC efficacy. MSCs were treated with the optimal doses of Crocin (Cr.), Dexamethasone (Dex.), and their combination. The A549 cells line was pretreated with the optimal dose of the CEES to mimic the lung disease. Then, the affected A549 cells were exposed to the preconditioned MSCs and conditioned media, and then their survival rates were estimated by MTTor2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Annexin-V PI apoptosis test was conducted for MSCs and A549 cells. Reactive Oxygen Species (ROS) assay and Enzyme-linked immunosorbent assay (ELISA) test demonstrated the percentage of production of ROS and the cytokines levels in A549/CEES, respectively. The results revealed significant increases in Cr. + Dex. treated MSCs (P < .01) and A549 cells treated with MSCs-CM/Cr/Dex (P < .01) groups' survival. The apoptosis rate and ROS production were reduced in the MSCs-CM/Cr/Dex. Also, considerable decreases in IL-1β (P < .01) and IL-6 (P < .01) and a significant increase in IL-10 (P < .05) in treated A549/CEES by Cr/Dex and MSCs-CM/Cr/Dex supported the synergistic effects of Crocin and Dexamethasone.
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Affiliation(s)
- Vahid Jamshidi
- Chemical Injuries Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran 14359-44711, Iran
| | - Raheleh Halabian
- Applied Microbiology Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran 14359-44711, Iran
| | - Pardis Saeedi
- Applied Microbiology Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran 14359-44711, Iran
| | - Hasan Bagheri
- Chemical Injuries Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran 14359-44711, Iran
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13
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Yang C, Du XY, Luo W. Clinical application prospects and transformation value of dental follicle stem cells in oral and neurological diseases. World J Stem Cells 2023; 15:136-149. [PMID: 37181000 PMCID: PMC10173814 DOI: 10.4252/wjsc.v15.i4.136] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Revised: 01/18/2023] [Accepted: 03/21/2023] [Indexed: 04/26/2023] Open
Abstract
Since dental pulp stem cells (DPSCs) were first reported, six types of dental SCs (DSCs) have been isolated and identified. DSCs originating from the craniofacial neural crest exhibit dental-like tissue differentiation potential and neuro-ectodermal features. As a member of DSCs, dental follicle SCs (DFSCs) are the only cell type obtained at the early developing stage of the tooth prior to eruption. Dental follicle tissue has the distinct advantage of large tissue volume compared with other dental tissues, which is a prerequisite for obtaining a sufficient number of cells to meet the needs of clinical applications. Furthermore, DFSCs exhibit a significantly higher cell proliferation rate, higher colony-formation capacity, and more primitive and better anti-inflammatory effects than other DSCs. In this respect, DFSCs have the potential to be of great clinical significance and translational value in oral and neurological diseases, with natural advantages based on their origin. Lastly, cryopreservation preserves the biological properties of DFSCs and enables them to be used as off-shelf products for clinical applications. This review summarizes and comments on the properties, application potential, and clinical transformation value of DFSCs, thereby inspiring novel perspectives in the future treatment of oral and neurological diseases.
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Affiliation(s)
- Chao Yang
- Research and Development Department, Shenzhen Uni-medica Technology Co., Ltd, Shenzhen 518051, Guangdong Province, China
- Department of Stomatology, The People’s Hospital of Longhua, Shenzhen 518109, Guangdong Province, China
| | - Xin-Ya Du
- Department of Stomatology, The People’s Hospital of Longhua, Shenzhen 518109, Guangdong Province, China
| | - Wen Luo
- Department of Stomatology, The First Affiliated Hospital of Hainan Medical University, Haikou 570102, Hainan Province, China
- School of Stomatology, Hainan Medical University, Haikou 571199, Hainan Province, China
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14
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Placental mesenchymal stem cells restore glucose and energy homeostasis in obesogenic adipocytes. Cell Tissue Res 2023; 391:127-144. [PMID: 36227376 DOI: 10.1007/s00441-022-03693-y] [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: 12/08/2021] [Accepted: 09/14/2022] [Indexed: 01/18/2023]
Abstract
Obesity (Ob) depicts a state of energy imbalance(s) being characterized by the accumulation of excessive fat and which predisposes to several metabolic diseases. Mesenchymal stem cells (MSCs) represent a promising option for addressing obesity and its associated metabolic co-morbidities. The present study aims at assessing the beneficial effects of human placental MSCs (P-MSCs) in mitigating Ob-associated insulin resistance (IR) and mitochondrial dysfunction both in vivo and in vitro. Under obesogenic milieu, adipocytes showed a significant reduction in glucose uptake, and impaired insulin signaling with decreased expression of UCP1 and PGC1α, suggestive of dysregulated non-shivering thermogenesis vis-a-vis mitochondrial biogenesis respectively. Furthermore, obesogenic adipocytes demonstrated impaired mitochondrial respiration and energy homeostasis evidenced by reduced oxygen consumption rate (OCR) and blunted ATP/NAD+/NADP+ production respectively. Interestingly, co-culturing adipocytes with P-MSCs activated PI3K-Akt signaling, improved glucose uptake, diminished ROS production, enhanced mitochondrial OCR, improved ATP/NAD+/NADP+ production, and promoted beiging of adipocytes evidenced by upregulated expression of PRDM16, UCP1, and PGC1α expression. In vivo, P-MSCs administration increased the peripheral blood glucose uptake and clearance, and improved insulin sensitivity and lipid profile with a coordinated increase in the ratio of ATP/ADP and NAD+ and NADP+ in the white adipose tissue (WAT), exemplified in WNIN/GR-Ob obese mutant rats. In line with in vitro findings, there was a significant reduction in adipocyte hypertrophy, increased mitochondrial staining, and thermogenesis. Our findings advocate for a therapeutic application of P-MSCs for improving glucose and energy homeostasis, i.e., probably restoring non-shivering thermogenesis towards obesity management.
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15
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Flores AI, Pipino C, Jerman UD, Liarte S, Gindraux F, Kreft ME, Nicolas FJ, Pandolfi A, Tratnjek L, Giebel B, Pozzobon M, Silini AR, Parolini O, Eissner G, Lang-Olip I. Perinatal derivatives: How to best characterize their multimodal functions in vitro. Part C: Inflammation, angiogenesis, and wound healing. Front Bioeng Biotechnol 2022; 10:965006. [PMID: 35992360 PMCID: PMC9386263 DOI: 10.3389/fbioe.2022.965006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Accepted: 07/07/2022] [Indexed: 11/13/2022] Open
Abstract
Perinatal derivatives (PnD) are birth-associated tissues, such as placenta, umbilical cord, amniotic and chorionic membrane, and thereof-derived cells as well as secretomes. PnD play an increasing therapeutic role with beneficial effects on the treatment of various diseases. The aim of this review is to elucidate the modes of action of non-hematopoietic PnD on inflammation, angiogenesis and wound healing. We describe the source and type of PnD with a special focus on their effects on inflammation and immune response, on vascular function as well as on cutaneous and oral wound healing, which is a complex process that comprises hemostasis, inflammation, proliferation (including epithelialization, angiogenesis), and remodeling. We further evaluate the different in vitro assays currently used for assessing selected functional and therapeutic PnD properties. This review is a joint effort from the COST SPRINT Action (CA17116) with the intention to promote PnD into the clinics. It is part of a quadrinomial series on functional assays for validation of PnD, spanning biological functions, such as immunomodulation, anti-microbial/anti-cancer activities, anti-inflammation, wound healing, angiogenesis, and regeneration.
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Affiliation(s)
- Ana I. Flores
- Regenerative Medicine Group, Research Institute Hospital 12 de Octubre (imas12), Madrid, Spain
| | - Caterina Pipino
- Center for Advanced Studies and Technology (CAST), Department of Medical, Oral and Biotechnological Sciences, University G. d’Annunzio Chieti-Pescara, StemTech Group, Chieti, Italy
| | - Urška Dragin Jerman
- University of Ljubljana, Faculty of Medicine, Institute of Cell Biology, Ljubljana, Slovenia
| | - Sergio Liarte
- Laboratorio de Regeneración, Oncología Molecular y TGF-β, IMIB-Arrixaca, Murcia, Spain
| | - Florelle Gindraux
- Service de Chirurgie Maxillo-Faciale, Stomatologie et Odontologie Hospitalière, CHU Besançon, Besançon, France
- Laboratoire de Nanomédecine, Imagerie, Thérapeutique EA 466, Université Bourgogne Franche-Comté, Besançon, France
| | - Mateja Erdani Kreft
- University of Ljubljana, Faculty of Medicine, Institute of Cell Biology, Ljubljana, Slovenia
| | - Francisco J. Nicolas
- Laboratorio de Regeneración, Oncología Molecular y TGF-β, IMIB-Arrixaca, Murcia, Spain
| | - Assunta Pandolfi
- Center for Advanced Studies and Technology (CAST), Department of Medical, Oral and Biotechnological Sciences, University G. d’Annunzio Chieti-Pescara, StemTech Group, Chieti, Italy
| | - Larisa Tratnjek
- University of Ljubljana, Faculty of Medicine, Institute of Cell Biology, Ljubljana, Slovenia
| | - Bernd Giebel
- Institute for Transfusion Medicine, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Michela Pozzobon
- Department of Women’s and Children’s Health, University of Padova, Padova, Italy and Foundation Institute of Pediatric Research Fondazione Città Della Speranza, Padova, Italy
| | | | - Ornella Parolini
- Department of Life Science and Public Health, Università Cattolica del Sacro Cuore, Rome, Italy
- Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS, Rome, Italy
| | - Günther Eissner
- Systems Biology Ireland, School of Medicine, Conway Institute, University College Dublin, Dublin, Ireland
| | - Ingrid Lang-Olip
- Division of Cell Biology, Histology and Embryology, Gottfried Schatz Research Center, Medical University of Graz, Graz, Austria
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16
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Ling X, Wang T, Han C, Wang P, Liu X, Zheng C, Bi J, Zhou X. IFN-γ-Primed hUCMSCs Significantly Reduced Inflammation via the Foxp3/ROR-γt/STAT3 Signaling Pathway in an Animal Model of Multiple Sclerosis. Front Immunol 2022; 13:835345. [PMID: 35300342 PMCID: PMC8921983 DOI: 10.3389/fimmu.2022.835345] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Accepted: 01/31/2022] [Indexed: 11/13/2022] Open
Abstract
Our previous study showed that interferon gamma (IFN-γ) might enhance the immunosuppressive properties of mesenchymal stem cells (MSCs) by upregulating the expression of indoleamine 2,3-dioxygenease. Therefore, we treated experimental autoimmune encephalomyelitis (EAE) mice, an animal model of multiple sclerosis (MS), with IFN-γ-primed human umbilical cord MSCs (IFN-γ-hUCMSCs). This study aimed to investigate the potential therapeutic effects of IFN-γ-hUCMSCs transplantation and to identify the biological pathways involved in EAE mice. Firstly, the body weights and clinical scores of EAE mice were recorded before and after treatment. Then, the inflammatory cytokine levels in splenic cell supernatants were quantified by enzyme-linked immunosorbent assay. Finally, the mRNA expression levels of signal transducer and activator of transduction 3 (STAT3), retinoic acid-related orphan receptor gamma t (ROR-γt), and forkhead box P3 (Foxp3) were detected by quantitative reverse transcription polymerase chain reaction. We observed that IFN-γ-hUCMSCs transplantation significantly alleviated body weight loss and decreased the clinical scores of mice. Additionally, IFN-γ-hUCMSCs transplantation could regulate the production of inflammatory cytokines, interleukin (IL)-10 and IL-17, thereby showing more potent treatment efficacy than human umbilical cord MSCs (hUCMSCs) transplantation (p < 0.05). Compared with the EAE group, the expressions of STAT3 and ROR-γt in the transplantation groups were significantly decreased, but the expression of Foxp3 was significantly upregulated in the IFN-γ-hUCMSCs transplantation group compared to that in the hUCMSCs transplantation group. We assumed that IFN-γ-hUCMSCs may affect the balance of T helper 17 (Th17) cells/regulatory T cells (Tregs) through the Foxp3/ROR-γt/STAT3 signaling pathway to reduce the inflammatory response, thereby improving the clinical symptoms of EAE mice. Our study demonstrated that transplantation of IFN-γ-hUCMSCs could reduce inflammation in EAE mice via the Foxp3/ROR-γt/STAT3 signaling pathway, highlighting the therapeutic effects of IFN-γ-hUCMSCs in patients with MS.
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Affiliation(s)
- Xiao Ling
- Department of Gynaecology, the Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Teng Wang
- Department of Digestive Internal Medicine, the Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Chao Han
- Department of Neurosurgery, the Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Pin Wang
- Department of Neurology Medicine, the Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Xiaoli Liu
- Department of Hematology, the Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.,Institute of Biotherapy for Hematological Malignancies, Shandong University, Jinan, China.,Shandong University-Karolinska Institute Collaboration Laboratory for Stem Cell Research, Shandong University, Jinan, China
| | - Chengyun Zheng
- Department of Hematology, the Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.,Institute of Biotherapy for Hematological Malignancies, Shandong University, Jinan, China.,Shandong University-Karolinska Institute Collaboration Laboratory for Stem Cell Research, Shandong University, Jinan, China
| | - Jianzhong Bi
- Department of Neurology Medicine, the Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Xiaoyan Zhou
- Department of Neurology Medicine, the Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
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Sun W, Yan S, Yang C, Yang J, Wang H, Li C, Zhang L, Zhao L, Zhang J, Cheng M, Li X, Xu D. Mesenchymal Stem Cells-derived Exosomes Ameliorate Lupus by Inducing M2 Macrophage Polarization and Regulatory T Cell Expansion in MRL/lpr Mice. Immunol Invest 2022; 51:1785-1803. [PMID: 35332841 DOI: 10.1080/08820139.2022.2055478] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Previous studies have implicated that the transplantation of human umbilical cord mesenchymal stem cells (hUC-MSCs) effectively alleviates systemic lupus erythematosus (SLE) primarily due to immunomodulatory effects. However, little is known about the role of hUC-MSC-derived exosomes in SLE. This study is carried out to investigate the modifying effects of hUC-MSC-exosomes on the differentiation and function of immune cells in SLE. hUC-MSC-derived exosomes were extracted from the cultural supernatant of hUC-MSCs by ultrahigh speed centrifugation. Quantitative real-time polymerase chain reaction, western blot, enzyme-linked immunosorbent assay, and flow cytometry were performed to estimate the effect of hUC-MSC-derived exosomes on macrophage and regulatory T cell (Treg) polarization. In vivo, hUC-MSC-exosomes were injected intravenously into 28-week-old MRL/lpr mice. We had found that exosomes derived from hUC-MSC restrained the proliferation and inflammation of macrophages in vitro. Besides, MSC-exosomes inhibited CD68+M1 and HLA-DR+M1 but promoted CD206+M2 and CD163+M2 in vitro. Moreover, MRL/lpr mice administrated by intravenous injection of MSC-exosomes had less infiltration of CD14+CD11c+M1 cells but more CD14+CD163+M2 cells as well as Tregs in spleens compared with those in MRL/lpr mice treated by PBS. Additionally, MSC-exosomes could alleviate nephritis, liver and lung injuries of MRL/lpr mice. The survival of lupus mice could be improved after MSC-exosome treatment. This study has suggested that MSC-derived exosomes exert anti-inflammatory and immunomodulatory effects in SLE. MSC-exosomes ameliorate nephritis and other key organ injuries by inducing M2 macrophages and Tregs polarization. As natural nanocarriers, MSC-exosomes may serve as a promising cell-free therapeutic strategy for SLE.Abbreviations: SLE: Systemic lupus erythematosus; hUC-MSCs: Human umbilical cord mesenchymal stem cells; MSCs: Mesenchymal stem cells; qRT-PCR: Quantitative real-time polymerase chain reaction; ELISA: Enzyme-linked immunosorbent assay; Tregs: Regulatory cells; TNF-α: Tumor necrosis factor alfa; IL: Interleukin; COVID-19: Coronavirus disease 2019; pTHP-1: PMA-induced THP-1 macrophages; TEM: Transmission electron microscopy; LPS: Lipopolysaccharide; EVs: Extracellular vesicles; TRAF1: Tumor necrosis factor receptor-associated factor 1; IRAK1: Interferon-α-interleukin-1 receptor-associated kinase 1; NF-κB: Nuclear factor-κB; BLyS: B lymphocyte stimulator; APRIL: A proliferation-inducing ligand.
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Affiliation(s)
- Wenchang Sun
- Central Laboratory of the First Affiliated Hospital, Weifang Medical University, Weifang, Shandong, China
| | - Shushan Yan
- Department of Gastrointestinal and Anal Diseases Surgery of the Affiliated Hospital, Weifang Medical University, Weifang, Shandong, China
| | - Chunjuan Yang
- Central Laboratory of the First Affiliated Hospital, Weifang Medical University, Weifang, Shandong, China.,Department of Rheumatology of the First Affiliated Hospital, Weifang Medical University, Weifang, Shandong, China
| | - Jinghan Yang
- Central Laboratory of the First Affiliated Hospital, Weifang Medical University, Weifang, Shandong, China.,Department of Rheumatology of the First Affiliated Hospital, Weifang Medical University, Weifang, Shandong, China
| | - Hui Wang
- Central Laboratory of the First Affiliated Hospital, Weifang Medical University, Weifang, Shandong, China
| | - Chaoran Li
- Department of Rheumatology of the First Affiliated Hospital, Weifang Medical University, Weifang, Shandong, China
| | - Lili Zhang
- Central Laboratory of the First Affiliated Hospital, Weifang Medical University, Weifang, Shandong, China
| | - Lu Zhao
- Central Laboratory of the First Affiliated Hospital, Weifang Medical University, Weifang, Shandong, China
| | - Jiaojiao Zhang
- Central Laboratory of the First Affiliated Hospital, Weifang Medical University, Weifang, Shandong, China
| | - Min Cheng
- Department of Physiology, Weifang Medical University, Weifang, Shandong, China
| | - Xiangling Li
- Department of Nephrology of Affiliated Hospital, Weifang Medical University, Weifang, Shandong, China
| | - Donghua Xu
- Central Laboratory of the First Affiliated Hospital, Weifang Medical University, Weifang, Shandong, China.,Department of Rheumatology of the First Affiliated Hospital, Weifang Medical University, Weifang, Shandong, China
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18
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Li Y, Ren X, Zhang Z, Duan Y, Li H, Chen S, Shao H, Li X, Zhang X. Effect of small extracellular vesicles derived from IL-10-overexpressing mesenchymal stem cells on experimental autoimmune uveitis. Stem Cell Res Ther 2022; 13:100. [PMID: 35255957 PMCID: PMC8900327 DOI: 10.1186/s13287-022-02780-9] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Accepted: 02/16/2022] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Autoimmune uveitis is a sight-threatening intraocular inflammation mainly caused by immune dysregulation. The development of safe and effective therapeutic approaches is urgently needed. Small extracellular vesicles (sEVs) derived from mesenchymal stem cells (MSCs) have been demonstrated to inhibit autoimmune responses; however, the immunosuppressive effect of MSC-sEVs is too weak for clinical transfer. In the current study, we investigated the therapeutic effect of IL-10-overexpressing MSC-sEVs (sEV-IL10) on experimental autoimmune uveitis (EAU) and studied the underlying mechanism. METHODS Mice were randomly grouped and received a single tail vein injection of different sEVs (50 μg) or PBS on day 11 post-immunization. The clinical and histological scores were graded, and the percentage of T helper cell was measured. To investigate the effect of sEVs on the proliferation of T-cells and the differentiation of Th1, Th17 and Treg cells, T-cells were cocultured with sEVs under the corresponding culture conditions. After labeled with PKH-26, sEVs were traced both in vivo and in vitro. RESULTS Compared with normal or vector sEV-treated groups, mice in the sEV-IL10-treated group had lower clinical and histological scores with lower percentages of Th1 and Th17 cells in the eyes and higher percentages of Treg cells in the spleen and draining lymph nodes (LN). Furthermore, sEV-IL10 enhanced the suppressive effect of MSC-sEVs on the proliferation of T-cells and differentiation of Th1 and Th17 cells, whereas upregulated the differentiation of Treg cells. Both in vivo and in vitro experiments demonstrated that MSC-sEVs were rapidly enriched in target tissues and internalized by T-cells. CONCLUSION These results suggested that sEV-IL10 effectively ameliorates EAU by regulating the proliferation and differentiation of T-cells, indicating sEVs as a potential novel therapy for autoimmune uveitis or other autoimmune diseases.
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Affiliation(s)
- Yongtao Li
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China
| | - Xinjun Ren
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China
| | - Zhihui Zhang
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China
| | - Yanan Duan
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China
| | - Huan Li
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China
| | - Shuang Chen
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China
| | - Hui Shao
- Department of Ophthalmology and Visual Sciences, Kentucky Lions Eye Center, University of Louisville, School of Medicine, Louisville, KY, USA
| | - Xiaorong Li
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China
| | - Xiaomin Zhang
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China.
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Alvites R, Branquinho M, Sousa AC, Lopes B, Sousa P, Maurício AC. Mesenchymal Stem/Stromal Cells and Their Paracrine Activity-Immunomodulation Mechanisms and How to Influence the Therapeutic Potential. Pharmaceutics 2022; 14:381. [PMID: 35214113 PMCID: PMC8875256 DOI: 10.3390/pharmaceutics14020381] [Citation(s) in RCA: 64] [Impact Index Per Article: 21.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Revised: 01/31/2022] [Accepted: 02/04/2022] [Indexed: 02/07/2023] Open
Abstract
With high clinical interest to be applied in regenerative medicine, Mesenchymal Stem/Stromal Cells have been widely studied due to their multipotency, wide distribution, and relative ease of isolation and expansion in vitro. Their remarkable biological characteristics and high immunomodulatory influence have opened doors to the application of MSCs in many clinical settings. The therapeutic influence of these cells and the interaction with the immune system seems to occur both directly and through a paracrine route, with the production and secretion of soluble factors and extracellular vesicles. The complex mechanisms through which this influence takes place is not fully understood, but several functional manipulation techniques, such as cell engineering, priming, and preconditioning, have been developed. In this review, the knowledge about the immunoregulatory and immunomodulatory capacity of MSCs and their secretion products is revisited, with a special focus on the phenomena of migration and homing, direct cell action and paracrine activity. The techniques for homing improvement, cell modulation and conditioning prior to the application of paracrine factors were also explored. Finally, multiple assays where different approaches were applied with varying success were used as examples to justify their exploration.
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Affiliation(s)
- Rui Alvites
- Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente (ICETA) da Universidade do Porto, Praça Gomes Teixeira, Apartado 55142, 4051-401 Porto, Portugal; (R.A.); (M.B.); (A.C.S.); (B.L.); (P.S.)
- Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, nº 228, 4050-313 Porto, Portugal
| | - Mariana Branquinho
- Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente (ICETA) da Universidade do Porto, Praça Gomes Teixeira, Apartado 55142, 4051-401 Porto, Portugal; (R.A.); (M.B.); (A.C.S.); (B.L.); (P.S.)
- Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, nº 228, 4050-313 Porto, Portugal
| | - Ana C. Sousa
- Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente (ICETA) da Universidade do Porto, Praça Gomes Teixeira, Apartado 55142, 4051-401 Porto, Portugal; (R.A.); (M.B.); (A.C.S.); (B.L.); (P.S.)
- Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, nº 228, 4050-313 Porto, Portugal
| | - Bruna Lopes
- Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente (ICETA) da Universidade do Porto, Praça Gomes Teixeira, Apartado 55142, 4051-401 Porto, Portugal; (R.A.); (M.B.); (A.C.S.); (B.L.); (P.S.)
- Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, nº 228, 4050-313 Porto, Portugal
| | - Patrícia Sousa
- Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente (ICETA) da Universidade do Porto, Praça Gomes Teixeira, Apartado 55142, 4051-401 Porto, Portugal; (R.A.); (M.B.); (A.C.S.); (B.L.); (P.S.)
- Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, nº 228, 4050-313 Porto, Portugal
| | - Ana Colette Maurício
- Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente (ICETA) da Universidade do Porto, Praça Gomes Teixeira, Apartado 55142, 4051-401 Porto, Portugal; (R.A.); (M.B.); (A.C.S.); (B.L.); (P.S.)
- Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, nº 228, 4050-313 Porto, Portugal
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20
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Mrahleh MA, Matar S, Jafar H, Wehaibi S, Aslam N, Awidi A. Human Wharton's Jelly-Derived Mesenchymal Stromal Cells Primed by Tumor Necrosis Factor-α and Interferon-γ Modulate the Innate and Adaptive Immune Cells of Type 1 Diabetic Patients. Front Immunol 2021; 12:732549. [PMID: 34650558 PMCID: PMC8506215 DOI: 10.3389/fimmu.2021.732549] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Accepted: 09/06/2021] [Indexed: 12/12/2022] Open
Abstract
The unique immunomodulation and immunosuppressive potential of Wharton’s jelly-derived mesenchymal stromal cells (WJ-MSCs) make them a promising therapeutic approach for autoimmune diseases including type 1 diabetes (T1D). The immunomodulatory effect of MSCs is exerted either by cell-cell contact or by secretome secretion. Cell-cell contact is a critical mechanism by which MSCs regulate immune-responses and generate immune regulatory cells such as tolerogenic dendritic cells (tolDCs) and regulatory T cell (Tregs). In this study, we primed WJ-MSCs with TNF-α and IFN-γ and investigated the immunomodulatory properties of primed WJ-MSCs on mature dendritic cells (mDCs) and activated T cells differentiated from mononuclear cells (MNCs) of T1D patient’s. Our findings revealed that primed WJ-MSCs impaired the antigen-mediated immunity, upregulated immune-tolerance genes and downregulated immune-response genes. We also found an increase in the production of anti-inflammatory cytokines and suppression of the production of pro-inflammatory cytokines. Significant upregulation of FOXP3, IL10 and TGFB1 augmented an immunosuppressive effect on adaptive T cell immunity which represented a strong evidence in support of the formation of Tregs. Furthermore, upregulation of many critical genes involved in the immune-tolerance mechanism (IDO1 and PTGES2/PTGS) was detected. Interestingly, upregulation of ENTPD1/NT5E genes express a strong evidence to switch immunostimulatory response toward immunoregulatory response. We conclude that WJ-MSCs primed by TNF-α and IFN-γ may represent a promising tool to treat the autoimmune disorders and can provide a new evidence to consider MSCs- based therapeutic approach for the treatment of TID.
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Affiliation(s)
| | - Suzan Matar
- Department of Clinical Laboratory Science, The University of Jordan, School of Science, Amman, Jordan
| | - Hanan Jafar
- Cell Therapy Center, The University of Jordan, Amman, Jordan.,Department of Anatomy & Histology, The University of Jordan, School of Medicine, Amman, Jordan
| | - Suha Wehaibi
- Cell Therapy Center, The University of Jordan, Amman, Jordan
| | - Nazneen Aslam
- Cell Therapy Center, The University of Jordan, Amman, Jordan
| | - Abdalla Awidi
- Cell Therapy Center, The University of Jordan, Amman, Jordan.,Department of Hematology & Oncology, The University of Jordan, School of Medicine, Amman, Jordan
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21
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Valiulienė G, Zentelytė A, Beržanskytė E, Navakauskienė R. Metabolic Profile and Neurogenic Potential of Human Amniotic Fluid Stem Cells From Normal vs. Fetus-Affected Gestations. Front Cell Dev Biol 2021; 9:700634. [PMID: 34336852 PMCID: PMC8322743 DOI: 10.3389/fcell.2021.700634] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Accepted: 06/21/2021] [Indexed: 12/04/2022] Open
Abstract
Human amniotic fluid stem cells (hAFSCs) possess some characteristics with mesenchymal stem cells (MSCs) and embryonic stem cells and have a broader differentiation potential compared to MSCs derived from other sources. Although hAFSCs are widely researched, their analysis mainly involves stem cells (SCs) obtained from normal, fetus-unaffected gestations. However, in clinical settings, knowledge about hAFSCs from normal gestations could be poorly translational, as hAFSCs from healthy and fetus-diseased gestations may differ in their differentiation and metabolic potential. Therefore, a more thorough investigation of hAFSCs derived from pathological gestations would provide researchers with the knowledge about the general characteristics of these cells that could be valuable for further scientific investigations and possible future clinical applicability. The goal of this study was to look into the neurogenic and metabolic potential of hAFSCs derived from diseased fetuses, when gestations were concomitant with polyhydramnios and compare them to hAFSCs derived from normal fetuses. Results demonstrated that these cells are similar in gene expression levels of stemness markers (SOX2, NANOG, LIN28A, etc.). However, they differ in expression of CD13, CD73, CD90, and CD105, as flow cytometry analysis revealed higher expression in hAFSCs from unaffected gestations. Furthermore, hAFSCs from “Normal” and “Pathology” groups were different in oxidative phosphorylation rate, as well as level of ATP and reactive oxygen species production. Although the secretion of neurotrophic factors BDNF and VEGF was of comparable degree, as evaluated with enzyme-linked immunosorbent assay (ELISA) test, hAFSCs from normal gestations were found to be more prone to neurogenic differentiation, compared to hAFSCs from polyhydramnios. Furthermore, hAFSCs from polyhydramnios were distinguished by higher secretion of pro-inflammatory cytokine TNFα, which was significantly downregulated in differentiated cells. Overall, these observations show that hAFSCs from pathological gestations with polyhydramnios differ in metabolic and inflammatory status and also possess lower neurogenic potential compared to hAFSCs from normal gestations. Therefore, further in vitro and in vivo studies are necessary to dissect the potential of hAFSCs from polyhydramnios in stem cell-based therapies. Future studies should also search for strategies that could improve the characteristics of hAFSCs derived from diseased fetuses in order for those cells to be successfully applied for regenerative medicine purposes.
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Affiliation(s)
- Giedrė Valiulienė
- Department of Molecular Cell Biology, Institute of Biochemistry, Life Sciences Center, Vilnius University, Vilnius, Lithuania
| | - Aistė Zentelytė
- Department of Molecular Cell Biology, Institute of Biochemistry, Life Sciences Center, Vilnius University, Vilnius, Lithuania
| | - Elizabet Beržanskytė
- Department of Molecular Cell Biology, Institute of Biochemistry, Life Sciences Center, Vilnius University, Vilnius, Lithuania
| | - Rūta Navakauskienė
- Department of Molecular Cell Biology, Institute of Biochemistry, Life Sciences Center, Vilnius University, Vilnius, Lithuania
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22
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Maraldi T, Angeloni C, Prata C, Hrelia S. NADPH Oxidases: Redox Regulators of Stem Cell Fate and Function. Antioxidants (Basel) 2021; 10:973. [PMID: 34204425 PMCID: PMC8234808 DOI: 10.3390/antiox10060973] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2021] [Revised: 06/15/2021] [Accepted: 06/15/2021] [Indexed: 12/12/2022] Open
Abstract
One of the major sources of reactive oxygen species (ROS) generated within stem cells is the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase family of enzymes (NOXs), which are critical determinants of the redox state beside antioxidant defense mechanisms. This balance is involved in another one that regulates stem cell fate: indeed, self-renewal, proliferation, and differentiation are decisive steps for stem cells during embryo development, adult tissue renovation, and cell therapy application. Ex vivo culture-expanded stem cells are being investigated for tissue repair and immune modulation, but events such as aging, senescence, and oxidative stress reduce their ex vivo proliferation, which is crucial for their clinical applications. Here, we review the role of NOX-derived ROS in stem cell biology and functions, focusing on positive and negative effects triggered by the activity of different NOX isoforms. We report recent findings on downstream molecular targets of NOX-ROS signaling that can modulate stem cell homeostasis and lineage commitment and discuss the implications in ex vivo expansion and in vivo engraftment, function, and longevity. This review highlights the role of NOX as a pivotal regulator of several stem cell populations, and we conclude that these aspects have important implications in the clinical utility of stem cells, but further studies on the effects of pharmacological modulation of NOX in human stem cells are imperative.
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Affiliation(s)
- Tullia Maraldi
- Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Via del Pozzo 71, 41124 Modena, Italy;
| | - Cristina Angeloni
- School of Pharmacy, University of Camerino, Via Gentile III da Varano, 62032 Camerino, Italy;
| | - Cecilia Prata
- Department of Pharmacy and Biotechnology, Alma Mater Studiorum—University of Bologna, Via Irnerio 48, 40126 Bologna, Italy
| | - Silvana Hrelia
- Department for Life Quality Studies, Alma Mater Studiorum—University of Bologna, Corso d’Augusto 237, 47921 Rimini, Italy;
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23
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Dzobo K. Recent Trends in Multipotent Human Mesenchymal Stem/Stromal Cells: Learning from History and Advancing Clinical Applications. OMICS-A JOURNAL OF INTEGRATIVE BIOLOGY 2021; 25:342-357. [PMID: 34115524 DOI: 10.1089/omi.2021.0049] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Early cell biology reports demonstrated the presence of cells with stem-like properties in bone marrow, with both hematopoietic and mesenchymal lineages. Over the years, various investigations have purified and characterized mesenchymal stromal/stem cells (MSCs) from different human tissues as cells with multilineage differentiation potential under the appropriate conditions. Due to their appealing characteristics and versatile potentials, MSCs are leveraged in many applications in medicine such as oncology, bioprinting, and as recent as therapeutics discovery and innovation for COVID-19. To date, studies indicate that MSCs have varied differentiation capabilities into different cell types, and demonstrate immunomodulating and anti-inflammatory properties. Different microenvironments or niche for MSCs and their resulting heterogeneity may influence attendant cellular behavior and differentiation capacity. The potential clinical applications of MSCs and exosomes derived from these cells have led to an avalanche of research reports on their properties and hundreds of clinical trials being undertaken. There is ample reason to think, as discussed in this expert review that the future looks bright and promising for MSC research, with many clinical trials under way to ascertain their clinical utility. This review provides a synthesis of the latest advances and trends in MSC research to allow for broad and critically informed use of MSCs. Early observations of the presence of these cells in the bone marrow and their remarkable differentiation capabilities and immunomodulation are also presented.
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Affiliation(s)
- Kevin Dzobo
- International Center for Genetic Engineering and Biotechnology (ICGEB), Cape Town Component, Cape Town, South Africa.,Division of Medical Biochemistry and Institute of Infectious Disease and Molecular Medicine, Department of Integrative Biomedical Sciences, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
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