{"title":"Preliminary study on the preparation of lyophilized acellular nerve scaffold complexes from rabbit sciatic nerves with human umbilical cord mesenchymal stem cells.","authors":"Chuang Qian, Shang-Yu Guo, Zheng Xu, Zhi-Qiang Zhang, Hao-Dong Li, Hao Li, Xiong-Sheng Chen","doi":"10.4252/wjsc.v16.i12.1047","DOIUrl":"10.4252/wjsc.v16.i12.1047","url":null,"abstract":"<p><strong>Background: </strong>The gold standard of care for patients with severe peripheral nerve injury is autologous nerve grafting; however, autologous nerve grafts are usually limited for patients because of the limited number of autologous nerve sources and the loss of neurosensory sensation in the donor area, whereas allogeneic or xenografts are even more limited by immune rejection. Tissue-engineered peripheral nerve scaffolds, with the morphology and structure of natural nerves and complex biological signals, hold the most promise as ideal peripheral nerve \"replacements\".</p><p><strong>Aim: </strong>To prepare allogenic peripheral nerve scaffolds using a low-toxicity decellularization method, and use human umbilical cord mesenchymal stem cells (hUC-MSCs) as seed cells to cultivate scaffold-cell complexes for the repair of injured peripheral nerves.</p><p><strong>Methods: </strong>After obtaining sciatic nerves from New Zealand rabbits, an optimal acellular scaffold preparation scheme was established by mechanical separation, varying lyophilization cycles, and trypsin and DNase digestion at different times. The scaffolds were evaluated by hematoxylin and eosin (HE) and luxol fast blue (LFB) staining. The maximum load, durability, and elastic modulus of the acellular scaffolds were assessed using a universal material testing machine. The acellular scaffolds were implanted into the dorsal erector spinae muscle of SD rats and the scaffold degradation and systemic inflammatory reactions were observed at 3 days, 1 week, 3 weeks, and 6 weeks following surgery to determine the histocompatibility between xenografts. The effect of acellular scaffold extracts on fibroblast proliferation was assessed using an MTT assay to measure the cytotoxicity of the scaffold residual reagents. In addition, the umbilical cord from cesarean section fetuses was collected, and the Wharton's jelly (WJ) was separated into culture cells and confirm the osteogenic and adipogenic differentiation of mesenchymal stem cells (MSCs) and hUC-MSCs. The cultured cells were induced to differentiate into Schwann cells by the antioxidant-growth factor induction method, and the differentiated cells and the myelinogenic properties were identified.</p><p><strong>Results: </strong>The experiments effectively decellularized the sciatic nerve of the New Zealand rabbits. After comparing the completed acellular scaffolds among the groups, the optimal decellularization preparation steps were established as follows: Mechanical separation of the epineurium, two cycles of lyophilization-rewarming, trypsin digestion for 5 hours, and DNase digestion for 10 hours. After HE staining, no residual nuclear components were evident on the scaffold, whereas the extracellular matrix remained intact. LFB staining showed a significant decrease in myelin sheath composition of the scaffold compared with that before preparation. Biomechanical testing revealed that the maximum tensile strength, elastic modulu","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":"16 12","pages":"1047-1061"},"PeriodicalIF":3.6,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11669985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142903741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Dual role of extracellular vesicles in neurodegenerative diseases.","authors":"Arianna Scuteri, Elisabetta Donzelli","doi":"10.4252/wjsc.v16.i12.1002","DOIUrl":"10.4252/wjsc.v16.i12.1002","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) are cell-to-cell interaction tools that are attracting increasing interest in the literature in two opposing areas. In addition to their role in physiological development, there is growing evidence of their involvement in healing and protective processes. However, EVs also mediate pathological conditions, particularly contributing to the progression of several chronic diseases, such as neurodegenerative diseases. On the other hand, EVs also form the core of a new therapeutic strategy for neuroprotection, which is based on the administration of EVs derived from a wide range of donor cells. In particular, the possibility of obtaining numerous EVs from stem cells of different origins, which is feasible for therapeutic aims, is now under investigation. In this review, we focused on neurodegenerative diseases, in which EVs could have a propagative detrimental effect or could also be exploited to deliver protective factors. This review explores the different hypotheses concerning the dual role of EVs, with the aim of shedding light on the following question: Can vesicles be used to fight vesicle-propagated diseases?</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":"16 12","pages":"1002-1011"},"PeriodicalIF":3.6,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11669982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142903641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Application of autophagy in mesenchymal stem cells.","authors":"Min Chai, Chun-Yan Zhang, Shuai Chen, Da-Hai Xu","doi":"10.4252/wjsc.v16.i12.990","DOIUrl":"10.4252/wjsc.v16.i12.990","url":null,"abstract":"<p><p>In this editorial, we have taken an in-depth look at the article published by Wan <i>et al</i>. The study showed that preconditioning mesenchymal stem cells (MSCs) protected them against programmed cell death, and increased their survival rate and therapeutic potential. Autophagy, a type of programmed cell death, is a major intracellular degradation and recycling pathway that is crucial for maintaining cellular homeostasis, self-renewal, and pluripotency. We have explored the relationship between autophagy and MSCs to determine the role of autophagy in the therapeutic applications of MSCs.</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":"16 12","pages":"990-1001"},"PeriodicalIF":3.6,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11669988/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142903632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jing-Yi Ding, Tian-Tian Meng, Ruo-Lin Du, Xin-Bin Song, Yi-Xiang Li, Jing Gao, Ran Ji, Qing-Yong He
{"title":"Bibliometrics of trends in global research on the roles of stem cells in myocardial fibrosis therapy.","authors":"Jing-Yi Ding, Tian-Tian Meng, Ruo-Lin Du, Xin-Bin Song, Yi-Xiang Li, Jing Gao, Ran Ji, Qing-Yong He","doi":"10.4252/wjsc.v16.i12.1086","DOIUrl":"10.4252/wjsc.v16.i12.1086","url":null,"abstract":"<p><strong>Background: </strong>Myocardial fibrosis, a condition linked to several cardiovascular diseases, is associated with a poor prognosis. Stem cell therapy has emerged as a potential treatment option and the application of stem cell therapy has been studied extensively. However, a comprehensive bibliometric analysis of these studies has yet to be conducted.</p><p><strong>Aim: </strong>To map thematic trends, analyze research hotspots, and project future directions of stem cell-based myocardial fibrosis therapy.</p><p><strong>Methods: </strong>We conducted a bibliometric and visual analysis of studies in the Web of Science Core Collection using VOSviewer and Microsoft Excel. The dataset included 1510 articles published between 2001 and 2024. Countries, organizations, authors, references, keywords, and co-citation networks were examined to identify evolving research trends.</p><p><strong>Results: </strong>Our findings revealed a steady increase in the number of publications, with a projected increase to over 200 publications annually by 2030. Initial research focused on stem cell-based therapy, particularly for myocardial infarction and heart failure. More recently, there has been a shift toward cell-free therapy, involving extracellular vesicles, exosomes, and microRNAs. Key research topics include angiogenesis, inflammation, apoptosis, autophagy, and oxidative stress.</p><p><strong>Conclusion: </strong>This analysis highlights the evolution of stem cell therapies for myocardial fibrosis, with emerging interest in cell-free approaches. These results are expected to guide future scientific exploration and decision-making.</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":"16 12","pages":"1086-1105"},"PeriodicalIF":3.6,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11669986/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142903637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mesenchymal stem cell therapy in atherosclerosis: A bibliometric and visual analysis.","authors":"Xing Cheng, Ya-Ling Li, Heng Wang, Rui-Jing Zhang, Ke-Yi Fan, Xiao-Tong Qi, Guo-Ping Zheng, Hong-Lin Dong","doi":"10.4252/wjsc.v16.i12.1062","DOIUrl":"10.4252/wjsc.v16.i12.1062","url":null,"abstract":"<p><strong>Background: </strong>Mesenchymal stem cells (MSCs) are capable of self-renewal and differentiation, and extensive studies have demonstrated their therapeutic potential in atherosclerosis (AS).</p><p><strong>Aim: </strong>To conduct a bibliometric analysis of studies on the use of MSC therapy for AS over the past two decades, assess key trends and provide insights for future research directions.</p><p><strong>Methods: </strong>We systematically searched the Web of Science Core Collection database for articles published between 1999 and 2023, yielding a total of 556 articles. Visual representation and bibliometric analysis of information and trends were facilitated using CiteSpace, the R package 'bibliometrix' and VOSviewer.</p><p><strong>Results: </strong>The analyzed articles were predominantly from 52 countries/regions, with prominent contributions from China and the United States. A cohort of 3057 authors contributed to these publications, with the works of Libby P distinguished by their influence and citation count. <i>Int J Mol Sci</i> has emerged as the journal with the highest publication volume, prominently disseminating influential papers and identifying citation outbreaks. Furthermore, our analysis identified current research hotspots within the field, focusing on vascular progenitor cells, inflammatory mechanisms, and extracellular vesicles. Emerging research frontiers, such as extracellular vesicles and oxidative stress, have been highlighted as areas of burgeoning interest. Finally, we offer perspectives on the status of research and future directions of MSC therapy in AS.</p><p><strong>Conclusion: </strong>This comprehensive analysis provides valuable insights for advancing scientific research on MSC therapy for AS. By elucidating pivotal trends and research directions, this study aimed to foster innovation and promote the progress of disciplines in this field, thereby contributing to advancing scientific knowledge and clinical practice.</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":"16 12","pages":"1062-1085"},"PeriodicalIF":3.6,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11669984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142903719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Preliminary evidence of renal function improvement in chronic progressive kidney disease using autologous CD34<sup>+</sup> cell therapy: A clinical trial.","authors":"Takayasu Ohtake, Tsutomu Sato, Toshitaka Tsukiyama, Suguru Muraoka, Ayaka Mitomo, Haruka Maruyama, Mizuki Yamano, Yasuhiro Mochida, Kunihiro Ishioka, Machiko Oka, Hidekazu Moriya, Sumi Hidaka, Haruchika Masuda, Takayuki Asahara, Shuzo Kobayashi","doi":"10.4252/wjsc.v16.i12.1012","DOIUrl":"10.4252/wjsc.v16.i12.1012","url":null,"abstract":"<p><strong>Background: </strong>To date, no specific treatment has been established to reverse progressive chronic kidney disease (CKD).</p><p><strong>Aim: </strong>To evaluate the safety and efficacy of autologous CD34<sup>+</sup> cell transplantation in CKD patients who exhibited a progressive decline in renal function.</p><p><strong>Methods: </strong>The estimated glomerular filtration rate (eGFR) at the beginning of the study was 15.0-28.0 mL/minute/1.73 m<sup>2</sup>. After five days of treatment with the granulocyte colony-stimulating factor, mononuclear cells were harvested and CD34<sup>+</sup> cells were magnetically collected. CD34<sup>+</sup> cells were directly injected into the bilateral renal arteries twice (at 0 and 3 months), and their safety and efficacy were evaluated for 6 months.</p><p><strong>Results: </strong>Four patients were enrolled and completed the study. Three of four patients showed improvement in eGFR slope (eGFR slope > 0 mL/minute/1.73 m<sup>2</sup>), with the monthly slope of eGFR (delta eGFR) changing from -1.36 ± 1.1 (pretreatment) to +0.22 ± 0.71 (at 6 months) mL/minute/1.73 m<sup>2</sup>/month (<i>P</i> = 0.135) after cell therapy. Additionally, intrarenal resistive index (<i>P</i> = 0.004) and shear wave velocity (<i>P</i> = 0.04) were significantly improved after cell therapy. One patient experienced transient fever after cell therapy, and experienced bone pain during granulocyte colony-stimulating factor administration. However, no severe adverse events were reported.</p><p><strong>Conclusion: </strong>In conclusion, our findings suggest that repetitive peripheral blood-derived autologous CD34<sup>+</sup> cell transplantation into the renal arteries is safe, feasible, and may be effective for patients with progressive CKD. However, a large-scale clinical trial is warranted to validate the efficacy of repetitive regenerative cell therapy using autologous CD34<sup>+</sup> cells in patients with progressive CKD.</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":"16 12","pages":"1012-1021"},"PeriodicalIF":3.6,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11669983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142903736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ji-Gang He, Xin-Xin Wu, Si Li, Dan Yan, Gao-Peng Xiao, Fu-Gang Mao
{"title":"Exosomes derived from microRNA-540-3p overexpressing mesenchymal stem cells promote immune tolerance <i>via</i> the CD74/nuclear factor-kappaB pathway in cardiac allograft.","authors":"Ji-Gang He, Xin-Xin Wu, Si Li, Dan Yan, Gao-Peng Xiao, Fu-Gang Mao","doi":"10.4252/wjsc.v16.i12.1022","DOIUrl":"10.4252/wjsc.v16.i12.1022","url":null,"abstract":"<p><strong>Background: </strong>Heart transplantation is a crucial intervention for severe heart failure, yet the challenge of organ rejection is significant. Bone marrow mesenchymal stem cells (BMSCs) and their exosomes have demonstrated potential in modulating T cells, dendtitic cells (DCs), and cytokines to achieve immunomodulatory effects. DCs, as key antigen-presenting cells, play a critical role in shaping immune responses by influencing T-cell activation and cytokine production. Through this modulation, BMSCs and their exosomes enhance graft tolerance and prolonging survival.</p><p><strong>Aim: </strong>To explore the immunomodulatory effects of exosomes derived from BMSCs overexpressing microRNA-540-3p (miR-540-3p) on cardiac allograft tolerance, focusing on how these exosomes modulating DCs and T cells activity through the CD74/nuclear factor-kappaB (NF-κB) pathway.</p><p><strong>Methods: </strong>Rat models were used to assess the impact of miR-540-3p-enhanced exosomes on immune tolerance in cardiac allografts. MiR-540-3p expression was manipulated in BMSCs, and derived exosomes were collected and administered to the rat models post-heart transplantation. The study monitored expression levels of major histocompatibility complex II, CD80, CD86, and CD274 in DCs, and quantified CD4<sup>+</sup> and CD8<sup>+</sup> T cells, T regulatory cells, and cytokine profiles.</p><p><strong>Results: </strong>Exosomes from miR-540-3p-overexpressing BMSCs lead to reduced expression of immune activation markers CD74 and NF-κB p65 in DCs and T cells. Rats treated with these exosomes showed decreased inflammation and improved cardiac function, indicated by lower levels of pro-inflammatory cytokines (interleukin-1β, interferon-γ) and higher levels of anti-inflammatory cytokines (interleukin-10, transforming growth factor β1). Additionally, miR-540-3p skewed the profiles of DCs and T cells towards immune tolerance, increasing the ratio of T regulatory cells and shifting cytokine secretion to favor graft acceptance.</p><p><strong>Conclusion: </strong>Exosomes derived from BMSCs overexpressing miR-540-3p significantly enhance immune tolerance and prolong cardiac allograft survival by modulating the CD74/NF-κB pathway, which regulates activities of DCs and T cells. These findings highlight a promising therapeutic strategy to improve heart transplantation outcomes and potentially reduce the need for prolonged immunosuppression.</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":"16 12","pages":"1022-1046"},"PeriodicalIF":3.6,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11669987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142903647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Interplay and therapeutic implications of colorectal cancer stem cells, tumor microenvironment, and gut microbiota.","authors":"Hui Zhang, Bo-Tao Xu, Di-Ping Luo, Tie-Fei He","doi":"10.4252/wjsc.v16.i12.1110","DOIUrl":"10.4252/wjsc.v16.i12.1110","url":null,"abstract":"<p><p>This article discusses the interplay between colorectal cancer (CRC) stem cells, tumor microenvironment (TME), and gut microbiota, emphasizing their dynamic roles in cancer progression and treatment resistance. It highlights the adaptability of CRC stem cells, the bidirectional influence of TME, and the multifaceted impact of gut microbiota on CRC. The manuscript proposes innovative therapeutic strategies focusing on these interactions, advocating for a shift towards personalized and ecosystem-targeted treatments in CRC. The conclusion underscores the importance of continued research in these areas for developing effective, personalized therapies.</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":"16 12","pages":"1110-1114"},"PeriodicalIF":3.6,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11669981/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142903702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Melatonin-based priming of stem cells to alleviate oxidative stress.","authors":"Khawaja Husnain Haider","doi":"10.4252/wjsc.v16.i11.985","DOIUrl":"https://doi.org/10.4252/wjsc.v16.i11.985","url":null,"abstract":"<p><p>Stem cell expansion <i>in vitro</i> and transplantation in the cytokine-rich proinflammatory milieu in the injured tissue generate immense oxidative stress that interferes with the cells' survival, stemness, and repairability. Stem cell priming has gained popularity to overcome these issues. Given melatonin's oxidative-scavenging properties, Gu <i>et al</i> have used periodontal ligament stem cells cultured under oxidative stress as an <i>in vitro</i> model to study the cytoprotective effects of melatonin. Our letter to the editor delves into melatonin-induced stem cell priming and the underlying molecular mechanism, focusing on the intriguing role of Yes-associated protein signaling in alleviating oxidative stress. We stress the importance of understanding the distinction between <i>in vitro</i> and <i>in vivo</i> oxidative stress conditions, a crucial aspect of stem cell research that invokes a sense of critical thinking in the readership. The study by Gu <i>et al</i> presents a novel approach to oxidative stress management, offering exciting possibilities for future research and applications.</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":"16 11","pages":"985-989"},"PeriodicalIF":3.6,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11606350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142772800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effects of miR-214-5p and miR-21-5p in hypoxic endometrial epithelial-cell-derived exosomes on human umbilical cord mesenchymal stem cells.","authors":"Wan-Yu Zhang, Han-Bi Wang, Cheng-Yan Deng","doi":"10.4252/wjsc.v16.i11.906","DOIUrl":"https://doi.org/10.4252/wjsc.v16.i11.906","url":null,"abstract":"<p><strong>Background: </strong>Thin endometrium seriously affects endometrial receptivity, resulting in a significant reduction in embryo implantation, and clinical pregnancy and live birth rates, and there is no gold standard for treatment. The main pathophysiological characteristics of thin endometrium are increased uterine arterial blood flow resistance, angiodysplasia, slow growth of the glandular epithelium, and low expression of vascular endothelial growth factor, resulting in endometrial epithelial cell (EEC) hypoxia and endometrial tissue aplasia. Human umbilical cord mesenchymal stem cells (HucMSCs) promote repair and regeneration of damaged endometrium by secreting microRNA (miRNA)-carrying exosomes. However, the initiation mechanism of HucMSCs to repair thin endometrium has not yet been clarified.</p><p><strong>Aim: </strong>To determine the role of hypoxic-EEC-derived exosomes in function of HucMSCs and explore the potential mechanism.</p><p><strong>Methods: </strong>Exosomes were isolated from normal EECs (EEC-exs) and hypoxia-damaged EECs (EECD-exs), before characterization using Western blotting, nanoparticle-tracking analysis, and transmission electron microscopy. HucMSCs were cocultured with EEC-exs or EECD-exs and differentially expressed miRNAs were determined using sequencing. MiR-21-5p or miR-214-5p inhibitors or miR-21-3p or miR-214-5p mimics were transfected into HucMSCs and treated with a signal transducer and activator of transcription 3 (STAT3) activator or STAT3 inhibitor. HucMSC migration was assessed by Transwell and wound healing assays. Differentiation of HucMSCs into EECs was assessed by detecting markers of stromal lineage (Vimentin and CD13) and epithelial cell lineage (CK19 and CD9) using Western blotting and immunofluorescence. The binding of the miRNAs to potential targets was validated by dual-luciferase reporter assay.</p><p><strong>Results: </strong>MiR-21-5p and miR-214-5p were lowly expressed in EECD-ex-pretreated HucMSCs. MiR-214-5p and miR-21-5p inhibitors facilitated the migratory and differentiative potentials of HucMSCs. MiR-21-5p and miR-214-5p targeted STAT3 and protein inhibitor of activated STAT3, respectively, and negatively regulated phospho-STAT3. MiR-21-5p- and miR-214-5p-inhibitor-induced promotive effects on HucMSC function were reversed by STAT3 inhibition. MiR-21-5p and miR-214-5p overexpression repressed HucMSC migration and differentiation, while STAT3 activation reversed these effects.</p><p><strong>Conclusion: </strong>Low expression of miR-21-5p/miR-214-5p in hypoxic-EEC-derived exosomes promotes migration and differentiation of HucMSCs into EECs <i>via</i> STAT3 signaling. Exosomal miR-214-5p/miR-21-5p may function as valuable targets for thin endometrium.</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":"16 11","pages":"906-925"},"PeriodicalIF":3.6,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11606348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142772714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}