World journal of stem cells最新文献

{"title":"MiR-126 regulates the effect of mesenchymal stem cell vascular repair on carotid atherosclerosis through MAPK/ERK signaling pathway.","authors":"Zi-Qiu Ye, Xiao-Hu Meng, Xin Fang, Han-Yi Liu, Hassan Hamisi Mwindadi","doi":"10.4252/wjsc.v17.i6.106520","DOIUrl":"10.4252/wjsc.v17.i6.106520","url":null,"abstract":"<p><strong>Background: </strong>Carotid atherosclerosis is a complex disease involving multiple cellular and molecular pathways. Mesenchymal stem cells (MSCs) show therapeutic potential, but their optimal targets and efficacy are still under study. MiR-126 enhances endothelial function and promotes angiogenesis by relieving vascular endothelial growth factor signaling suppression, suggesting its potential in vascular regeneration. However, its role in directing stem cell differentiation toward endothelial lineages remains unclear. We hypothesize that miR-126 may influence MSCs' immunomodulatory and vascular reparative functions <i>via</i> the mitogen-activated protein kinases/extracellular signal-regulated kinase (MAPK/ERK) pathway, thereby improving carotid atherosclerosis. This study explores this mechanism to provide novel insights and support the development of miR-126-based therapeutic strategies.</p><p><strong>Aim: </strong>To verify if miR-126 inhibits carotid atherosclerosis <i>via</i> the MAPK/ERK pathway.</p><p><strong>Methods: </strong>Rat bone marrow MSCs (product No. CP-R131, Wuhan, China) were verified by flow cytometry. The effects of miR-126 on MSCs' proliferation, migration, apoptosis, and cytokine expression were explored using microRNA mimics and inhibitors. Fluorescence staining quantified CD31+ cells to evaluate endothelial differentiation. <i>In vivo</i> differentiation was assessed, and MSCs were transplanted into a rat carotid artery balloon dilatation model. Rats were randomly divided into five groups: Control, negative control mimics, miR-126 mimics, negative control inhibitor, and miR-126 inhibitor.</p><p><strong>Results: </strong><i>In vitro</i>, MSCs treated with miR-126 mimics demonstrated enhanced proliferation, increased migration, and reduced apoptosis. These miR-126 mimics also significantly increased the secretion of vascular endothelial growth factor and basic fibroblast growth factor. Fluorescence and tissue staining indicated a higher proportion of CD31+ cells in the miR-126 mimics group. Additionally, the expression of endothelial-related genes (von Willebrand factor, endothelial nitric oxide synthase, and vascular endothelial-cadherin) was upregulated in this group. <i>In vivo</i>, miR-126-transfected MSCs effectively reduced neointimal thickness and promoted endothelial coverage in rats. MiR-126 stimulated MSC proliferation in a dose-dependent manner and reduced p38 and ERK1/2 phosphorylation. Conversely, miR-126 inhibition or blank controls resulted in opposing effects.</p><p><strong>Conclusion: </strong>MiR-126 exerts significant modulatory effects on the immunoregulatory and vascular reparative functions of MSCs through the MAPK/ERK signaling pathway, promoting their differentiation into endothelial cells and thereby mitigating atherosclerosis.</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":"17 6","pages":"106520"},"PeriodicalIF":3.6,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529913","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":"Clarifying the role of exosomal miR-137-3p in endometrial regeneration: Mechanistic gaps and future directions.","authors":"Fang Lin, Yue Ding, Ke-Xin Ma, Xiao-Ting Liang","doi":"10.4252/wjsc.v17.i6.109283","DOIUrl":"10.4252/wjsc.v17.i6.109283","url":null,"abstract":"<p><p>This article comments on the study by Zhang <i>et al</i>, which proposed that exosomes derived from hypoxia-injured endometrial epithelial cells promote human umbilical cord mesenchymal stem cell migration and differentiation into endometrial epithelial cells <i>via</i> exosomal miR-137-3p. The authors demonstrated that miR-137-3p targets ubiquitin protein ligase E3C and activates signal transducer and activator of transcription 3 signaling, thereby driving epithelial lineage transition. While this study expands our understanding of exosome-mediated intercellular communication in endometrial repair, several key gaps remain. Notably, microRNA (miRNA) profiling was performed in human umbilical cord mesenchymal stem cells post-exosome treatment, not in the exosomes derived from hypoxia-injured endometrial epithelial cell themselves, leaving open whether miR-137-3p is directly transferred or indirectly induced. In addition, data on exosome characterization were unavailable, and the rationale for selecting miR-137-3p over other differentially expressed miRNAs was not well justified. Future studies should include direct exosomal miRNA content analysis, <i>in vivo</i> validation, and deeper mechanistic exploration of the ubiquitin protein ligase E3C-signal transducer and activator of transcription 3 ubiquitination axis to establish the clinical and biological relevance of this pathway.</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":"17 6","pages":"109283"},"PeriodicalIF":3.6,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529891","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-based therapy for peripheral nerve injuries: A promise or reality?","authors":"Lucas Vinícius de Oliveira Ferreira, Kelly Cristine Santos Roballo, Rogério Martins Amorim","doi":"10.4252/wjsc.v17.i6.107833","DOIUrl":"10.4252/wjsc.v17.i6.107833","url":null,"abstract":"<p><p>Peripheral nerve injuries (PNI) that result in nerve gaps represent a major clinical challenge, frequently leading to long-term disability and a diminished quality of life for affected individuals. Despite advances in surgical techniques, functional recovery remains limited, highlighting the need for innovative therapeutic strategies. Mesenchymal stem cells (MSCs) have emerged as a promising avenue for nerve repair due to their regenerative, immunomodulatory, and neuroprotective properties. Thus, this review explored current approaches utilizing MSCs in the treatment of PNI, emphasizing their potential to enhance nerve regeneration and functional recovery. Furthermore, tissue engineering and transdifferentiation of MSCs into Schwann-like cells offer a versatile strategy to optimize therapeutic effects, paving the way for personalized medicine. Nevertheless, challenges persist regarding the clinical application of MSCs in PNI, including transplant safety, delivery methods, optimal dosing, and ethical considerations. A deeper understanding of the mechanisms underlying MSC action in PNI may contribute to more effective treatment protocols in the management of peripheral nerve defects.</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":"17 6","pages":"107833"},"PeriodicalIF":3.6,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529894","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-derived extracellular vesicles: Pioneering the next generation of biomedical applications.","authors":"Tong-Ming Liu","doi":"10.4252/wjsc.v17.i6.108197","DOIUrl":"10.4252/wjsc.v17.i6.108197","url":null,"abstract":"<p><p>Mesenchymal stem cell (MSC)-derived extracellular vesicles (MSC-EVs) represent the next generation of biomedical applications, offering advantages over MSCs such as higher stability and lower immunogenicity. As cell-free nanoparticles MSC-EVs have demonstrated both efficacy and safety in the treatment of a range of diseases. This article discussed the applications of MSC-EVs in hair regeneration, immunomodulation, and the treatment of acute kidney injury. MSC-EVs promote hair regeneration by enhancing dermal papilla cell proliferation and migration. They also modulate immune responses and mitigate inflammation through immune-related signaling pathways. Additionally, MSC-EVs contribute to improved renal function by modulating multiple signaling pathways. Despite these promising applications challenges remain in the clinical translation of MSC-EVs. Overcoming these challenges requires extensive research to fully optimize the therapeutic potential of MSC-EVs and advance their translation into clinical practice.</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":"17 6","pages":"108197"},"PeriodicalIF":3.6,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529896","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":"Fibro-adipogenic progenitors prevent skeletal muscle degeneration at acute phase upon tendon rupture in a murine tibialis anterior tenotomy model.","authors":"Zhe-Ci Ding, Juan-Juan He, Lu-Ze Shi, Jin Qian, Shu-Hao Mei, Xia Kang, Ji-Wu Chen","doi":"10.4252/wjsc.v17.i6.105491","DOIUrl":"10.4252/wjsc.v17.i6.105491","url":null,"abstract":"<p><strong>Background: </strong>Fibro-adipogenic progenitors (FAPs) are a group of mesenchymal stem cells that cause fibro-fatty degeneration in skeletal muscle in various chronic disease models. FAPs also play a role in preventing muscle degeneration at acute stages during disease progression. However, few studies have reported the changes in and function of FAPs in the acute phase after tendon rupture.</p><p><strong>Aim: </strong>To clarify the changes in the number of FAPs and their impact on skeletal muscle soon after tendon rupture to facilitate future studies targeting FAPs to treat muscle degeneration.</p><p><strong>Methods: </strong>We utilized Pdgfra-H2B::eGFP mice to trace and quantify FAPs in a tibialis anterior tenotomy (TAT) model at 0 and 3 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, and 6 weeks post-injury, and the results were further validated using fluorescence-activated cell sorting analysis with C57BL/6 mice at the same post-injury timepoints. We subsequently used PdgfraCre^ERT::Rosa^DTA mice, and evaluated the severity of post-TAT skeletal muscle degeneration with or without FAP-depletion.</p><p><strong>Results: </strong>The number of FAPs peaked at 1 week post-TAT before gradually declining to a level comparable to that pre-TAT. The change in the number of FAPs was potentially temporally correlated with the progression of skeletal muscle degeneration after TAT. FAP-depletion led to more severe degeneration early after TAT, indicating that FAPs potentially alleviate muscle degeneration after tendon rupture in the early post-injury phase.</p><p><strong>Conclusion: </strong>FAPs potentially alleviate the degeneration of skeletal muscle in the acute stage after tendon rupture.</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":"17 6","pages":"105491"},"PeriodicalIF":3.6,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203131/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529892","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":"Challenges in the clinical translation of stromal vascular fraction therapy in regenerative medicine.","authors":"Naveen Jeyaraman, Sandeep Shrivastava, Ravi Velamoor Rangarajan, Arulkumar Nallakumarasamy, Swaminathan Ramasubramanian, Avinash Gandi Devadas, Secunda Rupert, Madhan Jeyaraman","doi":"10.4252/wjsc.v17.i6.103775","DOIUrl":"10.4252/wjsc.v17.i6.103775","url":null,"abstract":"<p><p>Stromal vascular fraction (SVF) therapy is a promising regenerative medicine strategy derived from adipose tissue, containing a heterogeneous mix of cells, including adipose-derived stem, endothelial, and immune cells. Despite its potential in treating conditions like osteoarthritis, chronic wounds, and myocardial ischemia, significant challenges impede its clinical translation. Key obstacles include biological variability in SVF composition, unclear mechanisms of action, regulatory ambiguities, and the technical difficulty of ensuring standardized and scalable isolation methods. Furthermore, patient-specific factors, ethical concerns, and the need for comprehensive efficacy assessment complicate clinical application. Addressing these challenges requires advancements in technology, regulatory flexibility, interdisciplinary collaboration, and personalized therapeutic approaches. Innovations such as automated isolation systems, advanced biomaterials, and CRISPR-based gene editing are potential solutions to improve the therapeutic reliability of SVF. A structured roadmap, including preclinical research, regulatory approval, and post-market surveillance, is proposed to advance SVF therapies from the laboratory to clinical practice. Future directions should focus on large-scale clinical trials, biomarker development, real-world evidence generation, and standardization of protocols to enhance the safety, efficacy, and accessibility of SVF, ultimately realizing its potential as a versatile therapeutic in regenerative medicine.</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":"17 6","pages":"103775"},"PeriodicalIF":3.6,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529890","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 cells-derived exosomes alleviate radiation induced pulmonary fibrosis by inhibiting the protein kinase B/nuclear factor kappa B pathway.","authors":"Li-Li Wang, Ming-Yue Ouyang, Zi-En Yang, Si-Ning Xing, Song Zhao, Hui-Ying Yu","doi":"10.4252/wjsc.v17.i6.106488","DOIUrl":"10.4252/wjsc.v17.i6.106488","url":null,"abstract":"<p><strong>Background: </strong>Radiation induced pulmonary fibrosis (RIPF) is a long-term lung condition with a bleak outlook and few treatment possibilities. Mesenchymal stem cells (MSCs)-derived exosomes (MSCs-exosomes) possess tissue repair and regenerative properties, but their exact mechanisms in RIPF remain unclear. This study explores whether MSCs-exosomes can alleviate RIPF by modulating inflammation, extracellular matrix (ECM) accumulation, and epithelial-mesenchymal transition (EMT) <i>via</i> the protein kinase B (Akt)/nuclear factor kappa B (NF-κB) pathway.</p><p><strong>Aim: </strong>To assess the therapeutic potential and mechanisms of MSCs-exosomes in RIPF.</p><p><strong>Methods: </strong>Sprague-Dawley rats were received 30 Gy X-ray radiation on the right chest to induce RIPF, while RLE-6TN and BEAS-2B cell lines were exposed to 10 Gy X-rays. Using differential centrifugation, MSCs-exosomes were isolated, and their protective effects were examined both <i>in vivo</i> and <i>in vitro</i>. Inflammatory cytokine concentrations were measured using Luminex liquid chip detection and enzyme linked immunosorbent assay. ECM and EMT-related proteins were analyzed using immunohistochemistry, western blotting, and real-time quantitative polymerase chain reaction. Western blotting and immunohistochemistry were also used to investigate the mechanisms underlying MSCs-exosomes' effects in RIPF.</p><p><strong>Results: </strong>Administration of MSCs-exosomes significantly mitigated RIPF, reduced collagen deposition, and decreased levels of various inflammatory cytokines. Additionally, MSCs-exosomes prevented radiation-induced ECM accumulation and EMT. Treatment with MSCs-exosomes notably promoted cell proliferation, suppressed inflammation, and reversed ECM deposition and EMT in radiation-exposed alveolar epithelial cells. Mechanistic analysis further revealed that MSCs-exosomes exerted their anti-RIPF effects by inhibiting the Akt/NF-κB pathway, as shown in both <i>in vivo</i> and <i>in vitro</i> models.</p><p><strong>Conclusion: </strong>MSCs-exosomes mitigate RIPF by suppressing inflammation, ECM deposition, and EMT through Akt/NF-κB inhibition, highlighting their potential as a therapeutic strategy.</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":"17 6","pages":"106488"},"PeriodicalIF":3.6,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203132/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529897","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":"Reduced NRF2/Mfn2 activity promotes endoplasmic reticulum stress and senescence in adipose-derived mesenchymal stem cells in hypertrophic obese mice.","authors":"Jia Fang","doi":"10.4252/wjsc.v17.i6.104367","DOIUrl":"10.4252/wjsc.v17.i6.104367","url":null,"abstract":"<p><strong>Background: </strong>Hypertrophy obesity is closely associated with obesity-related metabolic diseases. The senescence of adipose-derived mesenchymal stem cells (ASCs) is believed to play a significant role in the development of hypertrophy obesity.</p><p><strong>Aim: </strong>To investigate the relationship between ASC senescence, endoplasmic reticulum (ER) stress, and nuclear factor erythroid-derived 2 (NRF2) activity in a mouse model of hypertrophy obesity. Additionally, we explored the mechanism through which NRF2 affects ASC senescence <i>via</i> mitofusin-2 (MFN2).</p><p><strong>Methods: </strong>We observed the senescent phenotype and ER stress (ERS) in ASCs from hypertrophic obese mouse models, and determined NRF2 activity. Chromatin immunoprecipitation-quantitative polymerase chain reaction (qPCR) was used to analyze the transcriptional activity of NRF2 on <i>Mfn2</i>. Additionally, co-immunoprecipitation experiments were conducted to investigate the interaction between MFN2 and binding immunoglobulin protein. The impact of NRF2 and MFN2 on the therapeutic effect of ASC transplantation against insulin resistance was explored through ASC transplantation.</p><p><strong>Results: </strong>The study found significant increases in senescence and ERS, accompanied by decreased NRF2 activity in ASCs from hypertrophic obese mouse models. Simultaneously, chromatin immunoprecipitation-qPCR analysis revealed a reduction in NRF2 transcriptional activity on <i>Mfn2</i>. The downregulation of NRF2 activity and <i>Mfn2</i> expression promoted senescence and ERS in ASCs, subsequently impacting the anti-insulin resistance effect of ASC transplantation. Furthermore, there exists a direct or indirect binding between MFN2 and binding immunoglobulin protein.</p><p><strong>Conclusion: </strong>The research outcomes suggest that NRF2 may regulate ERS and senescence in subcutaneous ASCs of hypertrophic obese mice by modulating <i>Mfn2</i>. These discoveries offer new insights into understanding metabolic diseases associated with hypertrophic obesity and potentially provide a foundation for intervention strategies.</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":"17 6","pages":"104367"},"PeriodicalIF":3.6,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529914","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-derived exosomes and the Wnt/β-catenin pathway: Unifying mechanisms of multi-organ regeneration and the path to precision clinical translation.","authors":"Xiong Yan, Ya-Xiong Guo, Yu-Xiang Liu, Chun Liu","doi":"10.4252/wjsc.v17.i6.106902","DOIUrl":"10.4252/wjsc.v17.i6.106902","url":null,"abstract":"<p><p>In this editorial, we discuss the article by Fu Y <i>et al</i>, indicating that hair development is influenced by exosomes from human adipose-derived stem/stromal cell-mediated cell-to-cell communication <i>via</i> the Wnt/β-catenin pathway. In recent years, mesenchymal stem cells (MSCs) and MSC-derived exosomes (MSC-Exos) have emerged as a promising cell-free therapeutic strategy due to their robust regenerative capabilities across multiple tissues. MSC-Exos are enriched with bioactive molecules, including proteins, microRNAs, and growth factors, which activate critical signaling pathways, notably the Wnt/β-catenin pathway, to promote cell proliferation, differentiation, and tissue repair. This editorial systematically examines the application of MSC-Exos in regenerating diverse tissues such as hair follicles and kidney, lung, and cardiac muscle tissue. Central to their mechanism is the activation of the Wnt/β-catenin pathway, which drives cell cycle progression (<i>via</i> cyclin B1/cyclin-dependent kinase 1), suppresses apoptosis (through Bcl-2/Bax modulation), and attenuates fibrosis (by inhibiting transforming growth factor-β/alpha-smooth muscle actin). The challenges related to the clinical translation of exosome-based therapies, including standardization of isolation protocols, optimization of dosing and delivery methods, and safety evaluation, are discussed. The most important challenge is standardizing isolation protocols because exosomes obtained from different sources or treatment methods are different, which leads to differences in the therapeutic effects of exosomes. Overall, MSC-Exos provide an effective cell-free strategy for tissue repair and offer a robust foundation to develop personalized regenerative medicine.</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":"17 6","pages":"106902"},"PeriodicalIF":3.6,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203135/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529895","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":"Human umbilical cord mesenchymal stem cells reduce platelet α-granule release in rats <i>via</i> the AKT/MEK/ERK pathway during acute exposure to high-altitude hypoxia.","authors":"Bo Zhang, Bao-Dong Gao, Yuan Su, Wen-Jing Mi, Tong-Xu Zeng, Fei-Fei Ma, Xiao-Qin Ha","doi":"10.4252/wjsc.v17.i6.106272","DOIUrl":"10.4252/wjsc.v17.i6.106272","url":null,"abstract":"<p><strong>Background: </strong>While acute exposure to high-altitude hypoxic environments can lead to increased thrombosis risk, preventive measures are currently limited. Recently, human umbilical cord mesenchymal stem cell (hUC-MSC) transplantation has been found effective in preventing and treating various clinical conditions, including thrombotic diseases. Platelets are crucial for thrombus formation, and their α-granules are key determinants of platelet function. However, little is known about the influence of hUC-MSCs on platelet α-granules.</p><p><strong>Aim: </strong>To investigate the influence of hUC-MSCs on platelet α-granules in rats during acute exposure to high-altitude hypoxia.</p><p><strong>Methods: </strong>Rats were assigned to three groups, namely, low-altitude, high-altitude, and hUC-MSC-treated groups. The low-altitude group was pretreated with normal saline and housed at an altitude of 1500 m. Rats in the high-altitude group received similar pretreatment and were housed in a simulated hypobaric hypoxia chamber with an altitude of 6500 m and oxygen partial pressure of 7.7 kPa. hUC-MSC-treated rats were pretreated with hUC-MSCs and exposed to hypoxic conditions. Aortic blood was collected after three days to assess platelet counts and morphology and α-granule release.</p><p><strong>Results: </strong>Compared to the low-altitude group, the high-altitude group exhibited significantly higher platelet counts, plasma levels of von Willebrand factor, platelet factor 4, beta-thromboglobulin, as well as surface P-selectin (CD62p) and p-protein kinase B, p-mitogen-activated protein kinase, and p-extracellular-signal regulated kinase expression in platelets. Platelet morphology in the high-altitude group was irregular, with extended pseudopodia and increased α-granule densities. However, these changes were not apparent in the hUC-MSC-treated group.</p><p><strong>Conclusion: </strong>Acute exposure to high-altitude hypoxia increased platelet counts, altered platelet morphology, and increased α-granule density and release. These effects were mitigated by hUC-MSC treatment, mediated by the protein kinase B/mitogen-activated protein kinase/extracellular-signal regulated kinase pathway. The results indicate that hUC-MSCs may represent a promising and effective approach for the prevention and treatment of acute high-altitude-associated thrombosis, providing an experimental foundation for the development of clinical applications.</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":"17 6","pages":"106272"},"PeriodicalIF":3.6,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529893","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}