Stem Cells Translational Medicine最新文献

{"title":"Longitudinal Magnetic Resonance Imaging Tracking of Transplanted Neural Progenitor Cells in the Spinal Cord Utilizing the Bright-Ferritin Mechanism.","authors":"Zixiang Luo, Keyu Zhuang, Seong Jun Kim, Kyle D W Vollett, Zijian Lou, Jian Wang, Hai-Ying Mary Cheng, Mohamad Khazaei, Michael G Fehlings, Hai-Ling Margaret Cheng","doi":"10.1093/stcltm/szae016","DOIUrl":"10.1093/stcltm/szae016","url":null,"abstract":"<p><p>Human neural progenitor cells (hNPCs) hold promise for treating spinal cord injury. Studies to date have focused on improving their regenerative potential and therapeutic effect. Equally important is ensuring successful delivery and engraftment of hNPCs at the injury site. Unfortunately, no current imaging solution for cell tracking is compatible with long-term monitoring in vivo. The objective of this study was to apply a novel bright-ferritin magnetic resonance imaging (MRI) mechanism to track hNPC transplants longitudinally and on demand in the rat spinal cord. We genetically modified hNPCs to stably overexpress human ferritin. Ferritin-overexpressing (FT) hNPCs labeled with 0.2 mM manganese provided significant T1-induced bright contrast on in vitro MRI, with no adverse effect on cell viability, morphology, proliferation, and differentiation. In vivo, 2 M cells were injected into the cervical spinal cord of Rowett nude rats. MRI employed T1-weighted acquisitions and T1 mapping on a 3 T scanner. Conventional short-term cell tracking was performed using exogenous Mn labeling prior to cell transplantation, which displayed transient bright contrast on MRI 1 day after cell transplantation and disappeared after 1 week. In contrast, long-term cell tracking using bright-ferritin allowed on-demand signal recall upon Mn supplementation and precise visualization of the surviving hNPC graft. In fact, this new cell tracking technology identified 7 weeks post-transplantation as the timepoint by which substantial hNPC integration occurred. Spatial distribution of hNPCs on MRI matched that on histology. In summary, bright-ferritin provides the first demonstration of long-term, on-demand, high-resolution, and specific tracking of hNPCs in the rat spinal cord.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":"546-558"},"PeriodicalIF":5.4,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11165155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140065985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Curcumin Improves Functional Recovery of Ruptured Tendon by Promoting Tenogenesis via PI3K/Akt Signaling.","authors":"Zhan Zhang, Yiqun Zhang, Han Wang, Baolong Li, Rangjuan Cao, Yan Li, Shusen Cui, Weizhong Zhang","doi":"10.1093/stcltm/szae007","DOIUrl":"10.1093/stcltm/szae007","url":null,"abstract":"<p><strong>Objective: </strong>In our previous study, we found that local release of curcumin from nanomicelles prevents peritendinous adhesion during Achilles tendon healing. The aim of this study is to further investigate the signaling integrated by curcumin to direct the tenogenetic program of tendon stem cells contributing to tendon healing.</p><p><strong>Methods: </strong>A surgical model of tendon rupture and repair (TRR) was established in rats. Peritendinous adhesion and inflammation, biomechanical function, and expression of β-catenin and epithelial cellular adhesion molecule (EpCAM) were determined. A dataset was analyzed to investigate differentially expressed genes and enriched genes related to the signaling pathways. Tendon stem cells were treated with curcumin to investigate the cellular and molecular events as well as the signaling pathway.</p><p><strong>Results: </strong>In rat TRR model, curcumin treatment resulted in not only significantly decreased peritendinous inflammatory but also improved tendon functional recovery along with significantly increased expressions of EpCAM and β-catenin. Analysis of the dataset indicated that the enriched genes were positively related to differentiation pathways but negatively related to proliferation pathways. In rat tendon stem cells, curcumin treatment inhibited proliferation but promoted differentiation. Curcumin's antioxidative activity was associated with tenogenesis. The upregulated expression of tendon lineage-specific markers was dependent on phosphatidylinositol 3'-kinase/Akt (PI3K/Akt) pathway which could be a potential mechanism of tenogenesis of curcumin treatment.</p><p><strong>Conclusion: </strong>Curcumin could improve tendon functional recovery via promoting tenogenesis in addition to its antioxidant and anti-inflammatory activities. Curcumin induced differentiation of tendon stem/progenitor cell into tenocytes via PI3K/Akt signaling pathway. This finding provided evidence for the application of curcumin to prevent adhesion during tendon repair.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":"477-489"},"PeriodicalIF":5.4,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11092270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139932966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stem Cell Derived Extracellular Vesicle Therapy for Multiple Sclerosis, A Systematic Review and Meta-Analysis of Preclinical Studies.","authors":"Mehri Barabadi, Madison C B Paton, Naveen Kumar, Rebecca Lim, Natalie L Payne","doi":"10.1093/stcltm/szae011","DOIUrl":"10.1093/stcltm/szae011","url":null,"abstract":"<p><p>Stem cell therapy holds promise for multiple sclerosis (MS), with efficacy of different stem cell types reported across a range of preclinical MS animal models. While stem cell therapy has been approved for a small number of diseases in humans, extracellular vesicles (EVs) may provide an efficacious, cost-effective, and safer alternative to stem cell therapy. To this end, we conducted a systematic review with meta-analysis to assess the effectiveness of stem cell-derived secretome (EV and conditioned media (CM)) in animal models of MS. The data were extracted to calculate standardized mean differences for primary outcome measure of disease severity, using a random effect model. Additionally, several subgroup analyses were conducted to assess the impact of various study variables such as stem cell type and source, stem cell modification, route and time of administration, number of animals and animal's age, and EV isolation methods on secondary outcome. Publication quality and risk of bias were assessed. Overall, 19 preclinical studies were included in the meta-analysis where stem cell EV/CM was found to significantly reduce disease severity in EV-treated (SMD = 2, 95% CI: 1.18-2.83, P < .00001) and CM-treated animals (SMD = 2.58, 95% CI: 1.34-3.83, P < .00001) compared with controls. Our analysis indicated that stem cell secretome has a positive effect on reducing demyelination, systemic neuroinflammation, and disease severity in preclinical models of MS. These findings indicate a potential therapeutic effect that merits investigation and validation in clinical settings.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":"436-447"},"PeriodicalIF":5.4,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11092271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140176547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of FDA's HCT/P ZIKV Recommendations on Cord Blood Unit Eligibility and Utilization in a Large Public Cord Blood Bank.","authors":"Dana S Guggenheim, Joanne Kurtzberg, Beth H Shaz","doi":"10.1093/stcltm/szae008","DOIUrl":"10.1093/stcltm/szae008","url":null,"abstract":"<p><strong>Background: </strong>Cord blood units (CBUs) that are ineligible for licensure due to incomplete compliance with FDA recommendations may be used for hematopoietic stem cell transplantation under urgent medical need and an Investigational Drug Application. The largest reason for CBU donor ineligibility is Zika virus (ZIKV) risk. The study's objective was to analyze the impact of current FDA recommendations for ZIKA risk on a large public cord blood bank and propose updated recommendations.</p><p><strong>Methods: </strong>We performed a retrospective analysis of Carolinas Cord Blood Bank (CCBB), an FDA licensed public CBB, using data from January 1, 2016 to November 21, 2023 and compared FDA recommendations for transfusion transmitted infections (TTI) for blood products and relevant communicable disease agents or diseases for human cell, tissue, or cellular or tissue-based products (HCT/Ps).</p><p><strong>Results: </strong>CCBB: 9057 (84.3% licensed) CBUs were banked. 984/1682 (58.5%) of unlicensed CBUs had ZIKV risk. 22.0% of CBUs with ZIKV risk were from Hispanic parents, compared to 16.1% of all units. 31 of IND CBUs (11 due to ZIKV risk without reported ZIKV transmission) were safely infused. FDA Guidance: HCT/P ZIKV, HIV, and vCJD recommendations have not been updated since 2018 in contrast to FDA removal of ZIKV as a relevant TTI in 2021 and updating HIV and vCJD guidance related to TTI in 2023 and 2022, respectively.</p><p><strong>Discussion: </strong>The FDA should consider new data to revise the HCT/P donor eligibility recommendations, which will increase the number of eligible HCT/P donors, and potentially improve access to therapies for a more diverse patient population.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":"448-453"},"PeriodicalIF":6.0,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11092266/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140194551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Manufacturing Parameters for the Creation of Clinical-Grade Human-Induced Pluripotent Stem Cell Lines From Umbilical Cord Mesenchymal Stromal Cells.","authors":"Liziane Raquel Beckenkamp, Camila Gomes da Silva, Mônica Luiza Immig Von Hohendorff, Karolyn Sassi Ogliari","doi":"10.1093/stcltm/szae010","DOIUrl":"10.1093/stcltm/szae010","url":null,"abstract":"<p><p>Induced pluripotent stem cells (iPSCs) are reprogrammed cells with a remarkable capacity for unlimited expansion and differentiation into various cell types. Companies worldwide are actively engaged in developing clinical-grade iPSC lines to address the needs of regenerative medicine, immunotherapies, and precision medicine. However, ensuring the safety and quality of iPSCs is essential, with adherence to Good Manufacturing Practices (GMP) and ethical considerations being paramount. Perinatal cell and tissue banks, such as umbilical cord (UC) blood and tissue banks, are emerging as ideal sources for generating iPSCs due to their unique characteristics and GMP compliance. These banks provide access to immature cells with limited environmental exposure, known family and medical histories of donors, and readily available resources, thereby reducing the time and cost associated with personalized treatment strategies. This study describes the establishment of the first clinical-grade iPSC lines from umbilical cord mesenchymal stromal cells in Brazil. The process involved rigorous quality control measures, safety assessments, and adherence to regulatory standards, resulting in iPSCs with the necessary characteristics for clinical use, including sterility, genomic integrity, and stability. Importantly, the study contributes to the development of a Current Good Manufacturing Practice-compliant iPSC production pipeline in Brazil, using commercially available, chemically defined, and xeno-free products, along with validation by national outsourced laboratories, thereby facilitating the adoption of this technology within the country. The study emphasizes Brazil's contribution to the progress of translational medicine and the promotion of scientific advancements within the field of regenerative and precision medicine.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":"454-461"},"PeriodicalIF":6.0,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11092272/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139973516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Rejuvenation and Functional Restoration of Aged Adipose Stem Cells by DUXAP10 Knockdown via the Regulation of the miR-214-3p/RASSF5 Axis.","authors":"Sen Ren, Chengcheng Li, Hewei Xiong, Qian Wu, Xiaohui Wu, Zhongwei Xiong, Lixing Dong, Bing Shu, Wei Wei, Chao Ma, Xiang Li, Jincao Chen","doi":"10.1093/stcltm/szae015","DOIUrl":"10.1093/stcltm/szae015","url":null,"abstract":"<p><p>Adipose stem cell (ASC)-based therapies provide an encouraging option for tissue repair and regeneration. However, the function of these cells declines with aging, which limits their clinical transformation. Recent studies have outlined the involvement of long non-coding RNAs in stem cell aging. Here, we reanalyzed our published RNA sequencing (RNA-seq) data profiling differences between ASCs from young and old donors and identified a lncRNA named double homeobox A pseudogene 10 (DUXAP10) as significantly accumulated in aged ASCs. Knocking down DUXAP10 promoted stem cell proliferation and migration and halted cell senescence and the secretion of proinflammatory cytokines. In addition, DUXAP10 was located in the cytoplasm and functioned as a decoy for miR-214-3p. miR-214-3p was downregulated in aged ASCs, and its overexpression rejuvenated aged ASCs and reversed the harm caused by DUXAP10. Furthermore, Ras Association Domain Family Member 5 (RASSF5) was the target of miR-214-3p and was upregulated in aged ASCs. Overexpressing DUXAP10 and inhibiting miR-214-3p both enhanced RASSF5 content in ASCs, while DUXAP10 knockdown promoted the therapeutic ability of aged ASCs for skin wound healing. Overall, this study offers new insights into the mechanism of age-related ASC dysfunction and names DUXAP10 and miR-214-3p as potential targets for energizing aged stem cells.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":"462-476"},"PeriodicalIF":5.4,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11092281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140068677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in 3D Bioprinted Cardiac Tissue Using Stem Cell-Derived Cardiomyocytes.","authors":"Jacqueline M Bliley, Maria A Stang, Anne Behre, Adam W Feinberg","doi":"10.1093/stcltm/szae014","DOIUrl":"10.1093/stcltm/szae014","url":null,"abstract":"<p><p>The ultimate goal of cardiac tissue engineering is to generate new muscle to repair or replace the damaged heart. This requires advances in stem cell technologies to differentiate billions of cardiomyocytes, together with advanced biofabrication approaches such as 3D bioprinting to achieve the requisite structure and contractile function. In this concise review, we cover recent progress in 3D bioprinting of cardiac tissue using pluripotent stem cell-derived cardiomyocytes, key design criteria for engineering aligned cardiac tissues, and ongoing challenges in the field that must be addressed to realize this goal.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":"425-435"},"PeriodicalIF":5.4,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11092277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140176546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Agrin Inhibition in Enteric Neural Stem Cells Enhances Their Migration Following Colonic Transplantation.","authors":"Jessica L Mueller, Rhian Stavely, Richard A Guyer, Ádám Soos, Sukhada Bhave, Chris Han, Ryo Hotta, Nandor Nagy, Allan M Goldstein","doi":"10.1093/stcltm/szae013","DOIUrl":"10.1093/stcltm/szae013","url":null,"abstract":"<p><p>Regenerative cell therapy to replenish the missing neurons and glia in the aganglionic segment of Hirschsprung disease represents a promising treatment option. However, the success of cell therapies for this condition are hindered by poor migration of the transplanted cells. This limitation is in part due to a markedly less permissive extracellular environment in the postnatal gut than that of the embryo. Coordinated interactions between enteric neural crest-derived cells (ENCDCs) and their local environment drive migration along the embryonic gut during development of the enteric nervous system. Modifying transplanted cells, or the postnatal extracellular environment, to better recapitulate embryonic ENCDC migration could be leveraged to improve the engraftment and coverage of stem cell transplants. We compared the transcriptomes of ENCDCs from the embryonic intestine to that of postnatal-derived neurospheres and identified 89 extracellular matrix (ECM)-associated genes that are differentially expressed. Agrin, a heparin sulfate proteoglycan with a known inhibitory effect on ENCDC migration, was highly over-expressed by postnatal-derived neurospheres. Using a function-blocking antibody and a shRNA-expressing lentivirus, we show that inhibiting agrin promotes ENCDC migration in vitro and following cell transplantation ex vivo and in vivo. This enhanced migration is associated with an increased proportion of GFAP + cells, whose migration is especially enhanced.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":"490-504"},"PeriodicalIF":5.4,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11092276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139932965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Treatment of Refractory Vitiligo With Autologous Cultured Epithelium Grafting: A Real-World Retrospective Cohort Study.","authors":"Jian Li, Xuanhao Zeng, Shujun Chen, Luyan Tang, Qi Zhang, Minzi Lv, Weiling Lian, Jinqi Wang, Haozhen Lv, Yating Liu, Jiayi Shen, Taro Uyama, Fuyue Wu, Jinfeng Wu, Jinhua Xu","doi":"10.1093/stcltm/szae009","DOIUrl":"10.1093/stcltm/szae009","url":null,"abstract":"<p><strong>Background: </strong>Surgical intervention is the main therapy for refractory vitiligo. We developed a modified autologous cultured epithelial grafting (ACEG) technique for vitiligo treatment. Between January 2015 and June 2019, a total of 726 patients with vitiligo underwent ACEG in China, with patient characteristics and clinical factors being meticulously documented. Using a generalized linear mixed model, we were able to assess the association between these characteristics and the repigmentation rate.</p><p><strong>Results: </strong>ACEG demonstrated a total efficacy rate of 82.81% (1754/2118) in treating 726 patients, with a higher repigmentation rate of 64.87% compared to conventional surgery at 52.69%. Notably, ACEG showed a better response in treating segmental vitiligo, lesions on lower limbs, age ≤ 18, and stable period > 3 years. A keratinocyte:melanocyte ratio below 25 was found to be advantageous too. Single-cell RNA sequencing analysis revealed an increase in melanocyte count and 2 subclusters of keratinocytes after ACEG, which remained higher in repigmented sites even after 1 year.</p><p><strong>Conclusions: </strong>ACEG is a promising therapy for refractory vitiligo. Patient age, clinical type, lesion site, and stability before surgery influence repigmentation in ACEG. The mechanism of repigmentation after ACEG treatment is likely not confined to the restoration of melanocyte populations. It may also involve an increase in the number of keratinocytes that support melanocyte function within the affected area. These keratinocytes may aid the post-transplant survival and function of melanocytes by secreting cytokines and extracellular matrix components.</p><p><strong>Trial registration: </strong>registered with Chictr.org.cn (ChiCTR2100051405).</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":"415-424"},"PeriodicalIF":6.0,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11092269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140185641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Conditioned Medium From Stem Cells of Human Exfoliated Deciduous Teeth Alleviates Mouse Osteoarthritis by Inducing sFRP1-Expressing M2 Macrophages.","authors":"Linze Xia, Fumiya Kano, Noboru Hashimoto, Yao Liu, Tsendsuren Khurel-Ochir, Naoko Ogasawara, Cheng Ding, Yang Xu, Hideharu Hibi, Tomonori Iwasaki, Eiji Tanaka, Akihito Yamamoto","doi":"10.1093/stcltm/szae006","DOIUrl":"10.1093/stcltm/szae006","url":null,"abstract":"<p><p>Intravenous administration of conditioned medium from stem cells of human exfoliated deciduous teeth (SHED-CM) regenerates mechanically injured osteochondral tissues in mouse temporomandibular joint osteoarthritis (TMJOA). However, the underlying therapeutic mechanisms remain unclear. Here, we showed that SHED-CM alleviated injured TMJ by inducing anti-inflammatory M2 macrophages in the synovium. Depletion of M2 by Mannosylated Clodrosome abolished the osteochondral repair activities of SHED-CM. Administration of CM from M2-induced by SHED-CM (M2-CM) effectively ameliorated mouse TMJOA by inhibiting chondrocyte inflammation and matrix degradation while enhancing chondrocyte proliferation and matrix formation. Notably, in vitro, M2-CM directly suppressed the catabolic activities while enhancing the anabolic activities of interleukin-1β-stimulated mouse primary chondrocytes. M2-CM also inhibited receptor activator of nuclear factor NF-κB ligand-induced osteoclastogenesis in RAW264.7 cells. Secretome analysis of M2-CM and M0-CM revealed that 5 proteins related to anti-inflammation and/or osteochondrogenesis were enriched in M2-CM. Of these proteins, the Wnt signal antagonist, secreted frizzled-related protein 1 (sFRP1), was the most abundant and played an essential role in the shift to anabolic chondrocytes, suggesting that M2 ameliorated TMJOA partly through sFRP1. This study suggests that secretome from SHED exerted remarkable osteochondral regeneration activities in TMJOA through the induction of sFRP1-expressing tissue-repair M2 macrophages.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":"399-413"},"PeriodicalIF":6.0,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11016837/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139747409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}