Stem Cell Research & Therapy最新文献

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Betaine enhances SCAPs chondrogenic differentiation and promotes cartilage repair in TMJOA through WDR81.
IF 7.1 2区 医学
Stem Cell Research & Therapy Pub Date : 2025-02-07 DOI: 10.1186/s13287-025-04161-4
Meiyue Wang, Zejie Wu, Xiaoyu Zheng, Yishu Huang, Yizhou Jin, Jiaxin Song, Wanzhen Lei, Hua Liu, Riyue Yu, Haoqing Yang, Runtao Gao
{"title":"Betaine enhances SCAPs chondrogenic differentiation and promotes cartilage repair in TMJOA through WDR81.","authors":"Meiyue Wang, Zejie Wu, Xiaoyu Zheng, Yishu Huang, Yizhou Jin, Jiaxin Song, Wanzhen Lei, Hua Liu, Riyue Yu, Haoqing Yang, Runtao Gao","doi":"10.1186/s13287-025-04161-4","DOIUrl":"10.1186/s13287-025-04161-4","url":null,"abstract":"<p><strong>Background: </strong>The cartilage tissue regeneration mediated with mesenchymal stem cells (MSCs) is considered as a viable strategy for temporomandibular joint osteoarthritis (TMJOA). Betaine has been confirmed to modulate the multidirectional differentiation of MSCs, while its effect on chondrogenic differentiation of Stem Cells from the Apical Papilla (SCAPs) is unknown. Here, we explored the effects and underlying mechanisms of betaine on chondrogenic differentiation of SCAPs.</p><p><strong>Methods: </strong>Betaine was added for SCAPs chondrogenic induction. The chondrogenic differentiation potential was assessed using Alcian Blue staining, Sirius Red staining and the main chondrogenic markers. In vivo cartilage regeneration effects were evaluated by the rat TMJOA model. RNA-sequencing and biological analyses were performed to select target genes and biological processes involved. The mechanism betaine acts on chondrogenic differentiation of SCAPs was further explored.</p><p><strong>Results: </strong>Betain-treated SCAPs demonstrated stronger cartilage regeneration in vitro and promoted cartilage repair of TMJOA in vivo. Betaine enhanced the expression of WDR81 in SCAPs during chondrogenesis. WDR81 overexpression promoted chondrogenic differentiation of SCAPs, while WDR81 depletion inhibited chondrogenic differentiation. In addition, both betaine treatment and WDR81 overexpression reduced intracellular reactive oxygen species levels and increased mitochondrial membrane potential in SCAPs.</p><p><strong>Conclusion: </strong>Betaine promotes SCAPs chondrogenic differentiation and provided an effective candidate for TMJOA treatment. WDR81 may serve as the potential drug target through mitophagy.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"55"},"PeriodicalIF":7.1,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11806766/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143371260","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}
引用次数: 0
Exosomes derived from liver failure patients' plasma stimulated mesenchymal stem cells alleviate acute liver failure.
IF 7.1 2区 医学
Stem Cell Research & Therapy Pub Date : 2025-02-07 DOI: 10.1186/s13287-025-04163-2
Zhuoran Wang, Jun Ling, Shaoli You, Bing Zhu
{"title":"Exosomes derived from liver failure patients' plasma stimulated mesenchymal stem cells alleviate acute liver failure.","authors":"Zhuoran Wang, Jun Ling, Shaoli You, Bing Zhu","doi":"10.1186/s13287-025-04163-2","DOIUrl":"10.1186/s13287-025-04163-2","url":null,"abstract":"<p><strong>Background: </strong>Exosomes derived from pre-stimulated mesenchymal stem cells (MSCs) have improved therapeutic effects in disease-associated microenvironments. In this study, we investigated the therapeutic potential of exosomes from MSCs stimulated with plasma from patients with liver failure (LF-Exos).</p><p><strong>Methods: </strong>Untreated exosomes (NC-Exos) and LF-Exos were extracted and characterized by nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), western blotting, and miRNA sequencing. We then examined the protective effects of LF-Exos on hepatocytes acutely injured by D-galactosamine (D-GalN)/lipopolysaccharide (LPS) co-treatment and on a mouse model of acute liver failure (ALF). Apoptosis was assessed using the CCK-8 assay and flow cytometry. Liver tissue damage was examined by hematoxylin and eosin staining and immunohistochemistry. The levels of signaling pathway proteins were determined by western blotting.</p><p><strong>Results: </strong>Stimulation with plasma from patients with liver failure significantly altered the morphology of MSCs and reduced their proliferative activity. Gene chip analysis identified 31 differentially expressed miRNAs, and further analysis showed that these differentially expressed miRNAs may affect the PI3K-AKT signaling pathway. Compared to NC-Exos, LF-Exos induced AKT phosphorylation in hepatocytes and liver tissues, inhibited D-GalN/LPS-induced apoptosis in hepatocytes, and reduced pathological liver injury in the mouse model of ALF.</p><p><strong>Conclusion: </strong>The biological effects of Exos were improved after stimulation with plasma from patients with liver failure. LF-Exos may inhibit the activity of the NLRP3 inflammasome and activate the PI3K-AKT signaling pathway to exert protective effects on acutely injured hepatocytes and a mouse model of ALF.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"48"},"PeriodicalIF":7.1,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11806533/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370975","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}
引用次数: 0
Mitochondrial transplantation for cardioprotection and induction of angiogenesis in ischemic heart disease.
IF 7.1 2区 医学
Stem Cell Research & Therapy Pub Date : 2025-02-07 DOI: 10.1186/s13287-025-04193-w
Parisa Hassanpour, Fatemeh Sadeghsoltani, Solmaz Saghebasl, Safieh Boroumand, Parisa Khanicheragh, Seyed Hossein Ahmadi Tafti, Reza Rahbarghazi, Mohammad Rahmati
{"title":"Mitochondrial transplantation for cardioprotection and induction of angiogenesis in ischemic heart disease.","authors":"Parisa Hassanpour, Fatemeh Sadeghsoltani, Solmaz Saghebasl, Safieh Boroumand, Parisa Khanicheragh, Seyed Hossein Ahmadi Tafti, Reza Rahbarghazi, Mohammad Rahmati","doi":"10.1186/s13287-025-04193-w","DOIUrl":"10.1186/s13287-025-04193-w","url":null,"abstract":"<p><p>To date, the regenerative potential of mitochondrial transplantation (MT) has been extensively investigated under several pathologies. Among various cardiovascular diseases, ischemic heart disease (IHD), the most prevalent pathological condition in human medicine, is induced by coronary artery narrowing, or occlusion, leading to bulk necrotic changes and fibrosis within the myocardium. Data associated with the pro-angiogenic activity of mitochondria have not been completely elucidated in terms of cardiac tissue regeneration. Here, we aimed to highlight the recent studies and advantages related to the application of mitochondrial mass in the ischemic myocardium. How and by which mechanisms, mitochondria can reduce aberrant myocardial tissue remodeling via different pathways such as angiogenesis and de novo blood formation was discussed in detail. We hope that data from the current review article help us understand the molecular and cellular mechanisms by which transplanted mitochondria exert their regenerative properties in the ischemic myocardium.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"54"},"PeriodicalIF":7.1,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11806797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370977","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}
引用次数: 0
Decoding SFRP2 progenitors in sustaining tooth growth at single-cell resolution.
IF 7.1 2区 医学
Stem Cell Research & Therapy Pub Date : 2025-02-07 DOI: 10.1186/s13287-025-04190-z
Tianyuan Zhao, Qing Zhong, Zewen Sun, Xiaoyi Yu, Tianmeng Sun, Zhengwen An
{"title":"Decoding SFRP2 progenitors in sustaining tooth growth at single-cell resolution.","authors":"Tianyuan Zhao, Qing Zhong, Zewen Sun, Xiaoyi Yu, Tianmeng Sun, Zhengwen An","doi":"10.1186/s13287-025-04190-z","DOIUrl":"10.1186/s13287-025-04190-z","url":null,"abstract":"<p><strong>Background: </strong>Single-cell transcriptomics has revolutionized tooth biology by uncovering previously unexplored areas. The mouse is a widely used model for studying human tissues and diseases, including dental pulp tissues. While human and mouse molars share many similarities, mouse incisors differ significantly from human teeth due to their continuous growth throughout their lifespan. The application of findings from mouse teeth to human disease remains insufficiently explored.</p><p><strong>Methods: </strong>Leveraging multiple single-cell datasets, we constructed a comprehensive dental pulp cell landscape to delineate tissue similarities and species-specific differences between humans and mice.</p><p><strong>Results: </strong>We identified a distinct cell population, Sfrp2<sup>hi</sup> fibroblast progenitors, found exclusively in mouse incisors and the developing tooth root of human molars. These cells play a crucial role in sustaining continuous tissue growth. Mechanistically, we found that the transcription factor Twist1, regulated via MAPK phosphorylation, binds to the Sfrp2 promoter and modulates Wnt signaling activation to maintain stem cell identity.</p><p><strong>Conclusions: </strong>Our study reveals a previously unrecognized subset of dental mesenchymal stem cells critical for tooth growth. This distinct subset, evolutionarily conserved between humans and mice, provides valuable insights into translational approaches for dental tissue regeneration and repair.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"58"},"PeriodicalIF":7.1,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11806734/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370963","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}
引用次数: 0
CircSPG21 ameliorates oxidative stress-induced senescence in nucleus pulposus-derived mesenchymal stem cells and mitigates intervertebral disc degeneration through the miR-217/SIRT1 axis and mitophagy.
IF 7.1 2区 医学
Stem Cell Research & Therapy Pub Date : 2025-02-07 DOI: 10.1186/s13287-025-04180-1
Yongbo Zhang, Sheng Yang, Xuan You, Zhengguang Li, Liuyang Chen, Rui Dai, Hua Sun, Liang Zhang
{"title":"CircSPG21 ameliorates oxidative stress-induced senescence in nucleus pulposus-derived mesenchymal stem cells and mitigates intervertebral disc degeneration through the miR-217/SIRT1 axis and mitophagy.","authors":"Yongbo Zhang, Sheng Yang, Xuan You, Zhengguang Li, Liuyang Chen, Rui Dai, Hua Sun, Liang Zhang","doi":"10.1186/s13287-025-04180-1","DOIUrl":"10.1186/s13287-025-04180-1","url":null,"abstract":"<p><strong>Background: </strong>The microenvironment of intervertebral disc degeneration (IVDD) is characterized by oxidative stress, leading to the senescence of nucleus pulposus-derived mesenchymal stem cells (NPMSCs). The purpose of this study was to investigate the competitive endogenous RNA mechanism involved in the senescence of NPMSCs induced by tert-butyl hydroperoxide (TBHP).</p><p><strong>Methods: </strong>Bioinformatic analysis identified differentially expressed circRNAs. Interactions among circSPG21, miR-217, and the NAD-dependent protein deacetylase sirtuin-1 (SIRT1) were validated through dual-luciferase assays, RNA fluorescence in situ hybridization and RNA immune precipitation. β-Gal staining, EdU staining, Western blotting, JC-1 assays, cell cycle analysis, and quantitative reverse transcription PCR (RT‒qPCR) were used to examine the functions of these molecules in TBHP-induced senescent NPMSCs. The therapeutic effects of circSPG21 were evaluated in a rat IVDD model.</p><p><strong>Results: </strong>CircSPG21 expression was significantly decreased in both human and rat IVDD tissues, whereas miR-217 was upregulated and SIRT1 was downregulated. Overexpression of circSPG21 alleviated NPMSC senescence by reducing P21 and P53 levels and restoring mitophagy through Parkin. The protective effects of circSPG21 were mediated through the miR-217/SIRT1 axis, as SIRT1 knockdown attenuated these benefits. CircSPG21 also ameliorated disc degeneration in the IVDD rat model, highlighting its potential as a therapeutic target.</p><p><strong>Conclusion: </strong>CircSPG21 reduces oxidative stress-induced NPMSC senescence through the miR-217/SIRT1 axis and mitophagy, providing new insights into IVDD and identifying circSPG21 as a potential therapeutic target for disc degeneration.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"49"},"PeriodicalIF":7.1,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11806878/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370288","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}
引用次数: 0
Mesenchymal stem cells-derived exosomes attenuate mouse non-heart-beating liver transplantation through Mir-17-5p-regulated Kupffer cell pyroptosis. 间充质干细胞衍生的外泌体通过Mir-17-5p调控的Kupffer细胞热解作用减弱小鼠非心脏跳动肝移植。
IF 7.1 2区 医学
Stem Cell Research & Therapy Pub Date : 2025-02-07 DOI: 10.1186/s13287-025-04169-w
Yang Tian, Ming Jin, Nanwei Ye, Zhenzhen Gao, Yuancong Jiang, Sheng Yan
{"title":"Mesenchymal stem cells-derived exosomes attenuate mouse non-heart-beating liver transplantation through Mir-17-5p-regulated Kupffer cell pyroptosis.","authors":"Yang Tian, Ming Jin, Nanwei Ye, Zhenzhen Gao, Yuancong Jiang, Sheng Yan","doi":"10.1186/s13287-025-04169-w","DOIUrl":"10.1186/s13287-025-04169-w","url":null,"abstract":"<p><strong>Background: </strong>Liver transplantation is the most effective treatment for end-stage liver disease. However, the shortage of donor livers has become a significant obstacle to the advancement of liver transplantation. Mesenchymal stem cells-derived exosomes (MSCs-Exo) have been extensively investigated in liver diseases. However, the underlying mechanisms of how they can protect organ donation after cardiac death (DCD) livers remain unclear.</p><p><strong>Methods: </strong>In this study, an arterialized mouse non-heart-beating (NHB) liver transplantation model was used to investigate the effect of MSCs-Exo on NHB liver transplantation. The survival rates, histology, pro-inflammatory cytokine and chemokine expression, and underlying mechanisms were investigated.</p><p><strong>Results: </strong>The infusion of MSCs-Exo reduced the injury to DCD liver graft tissue. In vitro and in vivo experiments demonstrated that MSCs-Exo could inhibit hydrogen peroxide-induced pyroptosis of Kupffer cells. We found that miR-17-5p was significantly abundant in MSCs-Exo, targeting and regulating the TXNIP expression. This action inhibited NLRP3-mediated pyroptosis of Kupffer cells through the classical Caspase1-dependent pathway, alleviating DCD liver graft injury.</p><p><strong>Conclusion: </strong>Our study elucidated a protective role for MSCs-Exo in a NHB liver transplantation model. This mechanism provides a theoretical basis and new strategies for the clinical application of MSCs-Exo to improve liver graft quality and alleviate the organ shortage in liver transplantation.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"57"},"PeriodicalIF":7.1,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11806715/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370976","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}
引用次数: 0
Enhanced myofibroblast differentiation of eMSCs in intrauterine adhesions.
IF 7.1 2区 医学
Stem Cell Research & Therapy Pub Date : 2025-02-04 DOI: 10.1186/s13287-025-04183-y
Jun Song, Meiqi Li, Yuan Tao, Yumeng Li, Canrong Mai, Jingting Zhang, Lan Yao, Shaoquan Shi, Jianyong Xu
{"title":"Enhanced myofibroblast differentiation of eMSCs in intrauterine adhesions.","authors":"Jun Song, Meiqi Li, Yuan Tao, Yumeng Li, Canrong Mai, Jingting Zhang, Lan Yao, Shaoquan Shi, Jianyong Xu","doi":"10.1186/s13287-025-04183-y","DOIUrl":"10.1186/s13287-025-04183-y","url":null,"abstract":"<p><strong>Background: </strong>Intrauterine adhesions (IUA) is one of the most common gynecological diseases and main causes of uterine infertility. Among proposed hypotheses on IUA development, the reduced endometrial regeneration resulting from loss of functional stem cells has been proposed as the key factor affecting the IUA prognosis. However, the underlying mechanisms mostly remain unclear. Because the eMSCs (endometrial mesenchymal stem/stromal cells) play a critical role in both supporting the gland development and also preparing the environment for embryo implantation through decidualization, the characteristics and functions were compared between the eMSCs derived from IUA and non-IUA patients, to uncover the important roles of eMSCs in IUA and also the underlying mechanisms.</p><p><strong>Methods: </strong>Endometrium biopsies were collected from IUA patients and controls. The fibrosis features and eMSC distributions were investigated with IHC (immunohistochemistry). Then the eMSCs were isolated and their functions and characteristics were analyzed in vitro.</p><p><strong>Results: </strong>Our results indicate that the scar tissues in IUA are characterized with hyper-activation of pro-fibrotic fibroblast and myo-differentiation, along with reduced number of eMSCs. The isolated eMSCs from IUA and controls show similar functions from the perspectives of cell morphology, proliferation, colony formation, exosome secretion, positive ratio of eMSC markers and conventional MSC markers, tri-differentiation efficiency, the ability of suppressing lymphocyte proliferation, cell aging, and promoting vascular tube formation. However, the eMSCs from IUA have reduced levels of decidualization and higher levels of cell migration, invasion, and also myofibroblast differentiation. Further investigations indicate that the TGF-β pathway, which is the major inducer of myofibroblast differentiation, is up-regulated and responsible for the enhanced myofibroblast differentiation potential of eMSCs from IUA.</p><p><strong>Conclusions: </strong>In conclusion, we have demonstrated here that the scar tissues in IUA biopsy are characterized with enhanced differentiation of pro-fibrotic fibroblast and myofibroblast. The number of eMSCs is reduced in IUA tissues, and their myofibroblast differentiation capability is increased.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"35"},"PeriodicalIF":7.1,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792338/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143123122","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}
引用次数: 0
hBMSC-EVs alleviate weightlessness-induced skeletal muscle atrophy by suppressing oxidative stress and inflammation.
IF 7.1 2区 医学
Stem Cell Research & Therapy Pub Date : 2025-02-04 DOI: 10.1186/s13287-025-04175-y
Mengyuan Chang, Ruiqi Liu, Bingqian Chen, Jin Xu, Wei Wang, Yanan Ji, Zihui Gao, Boya Liu, Xinlei Yao, Hualin Sun, Feng Xu, Yuntian Shen
{"title":"hBMSC-EVs alleviate weightlessness-induced skeletal muscle atrophy by suppressing oxidative stress and inflammation.","authors":"Mengyuan Chang, Ruiqi Liu, Bingqian Chen, Jin Xu, Wei Wang, Yanan Ji, Zihui Gao, Boya Liu, Xinlei Yao, Hualin Sun, Feng Xu, Yuntian Shen","doi":"10.1186/s13287-025-04175-y","DOIUrl":"10.1186/s13287-025-04175-y","url":null,"abstract":"<p><strong>Background: </strong>Muscle disuse and offloading in microgravity are likely the primary factors mediating spaceflight-induced muscle atrophy, for which there is currently no effective treatment other than exercise. Extracellular vesicles derived from bone marrow mesenchymal stem cells (BMSC-EVs) possess anti-inflammatory and antioxidant properties, offering a potential strategy for combating weightless muscular atrophy.</p><p><strong>Methods: </strong>In this study, human BMSCs-EVs (hBMSC-EVs) were isolated using super-centrifugation and characterized. C2C12 myotube nutrition-deprivation and mice tail suspension models were established. Subsequently, the diameter of C2C12 myotubes, Soleus mass, cross-sectional area (CSA) of muscle fibers, and grip strength in mice were assessed to investigate the impact of hBMSC-EVs on muscle atrophy. Immunostaining, transmission electron microscopy observation, and western blot analysis were employed to assess the impact of hBMSC-EVs on muscle fiber types, ROS levels, inflammation, ubiquitin-proteasome system activity, and autophagy lysosome pathway activation in skeletal muscle atrophy.</p><p><strong>Results: </strong>The active hBMSC-EVs can be internalized by C2C12 myotubes and skeletal muscle. hBMSC-EVs can effectively reduce C2C12 myotube atrophy caused by nutritional deprivation, with a concentration of 10 × 10<sup>8</sup> particles/mL showing the best effect (P < 0.001). Additionally, hBMSC-EVs can down-regulate the protein levels associated with UPS and oxidative stress. Moreover, intravenous administration of hBMSC-EVs at a concentration of 1 × 10<sup>10</sup> particles/mL can effectively reverse the reduction in soleus mass (P < 0.001), CSA (P < 0.01), and grip strength (P < 0.001) in mice caused by weightlessness. They demonstrate the ability to inhibit protein degradation mediated by UPS and autophagy lysosome pathway, along with the suppression of oxidative stress and inflammatory responses. Furthermore, hBMSC-EVs impede the transition of slow muscle fibers to fast muscle fibers via upregulation of Sirt1 and PGC-1α protein levels.</p><p><strong>Conclusions: </strong>Our findings indicate that hBMSC-EVs are capable of inhibiting excessive activation of the UPS and autophagy lysosome pathway, suppressing oxidative stress and inflammatory response, reversing muscle fiber type transformation, effectively delaying hindlimb unloading-induced muscle atrophy and enhancing muscle function. Our study has further advanced the understanding of the molecular mechanism underlying muscle atrophy in weightlessness and has demonstrated the protective effect of hBMSC-EVs on muscle atrophy.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"46"},"PeriodicalIF":7.1,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143123575","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}
引用次数: 0
Fate and long-lasting therapeutic effects of mesenchymal stromal/stem-like cells: mechanistic insights.
IF 7.1 2区 医学
Stem Cell Research & Therapy Pub Date : 2025-02-04 DOI: 10.1186/s13287-025-04158-z
Akram Hoseinzadeh, Seyed-Alireza Esmaeili, Reza Sahebi, Anahita Madani Melak, Mahmoud Mahmoudi, Maliheh Hasannia, Rasoul Baharlou
{"title":"Fate and long-lasting therapeutic effects of mesenchymal stromal/stem-like cells: mechanistic insights.","authors":"Akram Hoseinzadeh, Seyed-Alireza Esmaeili, Reza Sahebi, Anahita Madani Melak, Mahmoud Mahmoudi, Maliheh Hasannia, Rasoul Baharlou","doi":"10.1186/s13287-025-04158-z","DOIUrl":"10.1186/s13287-025-04158-z","url":null,"abstract":"<p><p>A large body of evidence suggests that mesenchymal stromal cells (MSCs) are able to respond rapidly to the cytokine milieu following systemic infusion. This encounter has the potential to dictate their therapeutic efficacy (also referred to as licensing). MSCs are able to rapidly react to cellular damage by migrating to the inflamed tissue and ultimately modifying the inflammatory microenvironment. However, the limited use of MSCs in clinical practice can be attributed to a lack of understanding of the fate of MSCs in patients after administration and long term MSC-derived therapeutic activity. While the known physiological effectors of viable MSCs make a relative contribution, an innate property of MSCs as a therapeutic agent is their caspase-dependent cell death. These mechanisms may be involving the functional reprogramming of myeloid phagocytes via efferocytosis, the process by which apoptotic bodies (ABs) are identified for engulfment by both specialized and non-specialized phagocytic cells. Recent studies have provided evidence that the uptake of ABs with a distinct genetic component can induce changes in gene expression through the process of epigenetic remodeling. This phenomenon, known as 'trained immunity', has a significant impact on immunometabolism processes. It is hypothesized that the diversity of recipient cells within the inflammatory stroma adjacent to MSCs may potentially serve as a biomarker for predicting the clinical outcome of MSC treatment, while also contributing to the variable outcomes observed with MSC-based therapies. Therefore, the long-term reconstructive process of MSCs may potentially be mediated by MSC apoptosis and subsequent phagocyte-mediated efferocytosis.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"33"},"PeriodicalIF":7.1,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792531/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143123569","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}
引用次数: 0
Progress on mitochondria and hair follicle development in androgenetic alopecia: relationships and therapeutic perspectives.
IF 7.1 2区 医学
Stem Cell Research & Therapy Pub Date : 2025-02-04 DOI: 10.1186/s13287-025-04182-z
Ting-Ru Dong, Yu-Jie Li, Shi-Yu Jin, Feng-Lan Yang, Ren-Xue Xiong, Ye-Qin Dai, Xiu-Zu Song, Cui-Ping Guan
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