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Reduced mechanical shear is associated with early cortical differentiation and GDNF-GFRA1/RET signalling in human brain organoids. 在人脑类器官中,机械剪切减少与早期皮层分化和GDNF-GFRA1/RET信号传导有关。
IF 5.9 2区 医学
Stem Cells Translational Medicine Pub Date : 2026-08-18 DOI: 10.1093/stcltm/szag070
Zizhen Zhao, Jingran Du, Shan Zhang, Haowen Shi, Hui Chen, Hong Cheng, Lihua Zhou, Chenju Yi, Jiachuan Wang
{"title":"Reduced mechanical shear is associated with early cortical differentiation and GDNF-GFRA1/RET signalling in human brain organoids.","authors":"Zizhen Zhao, Jingran Du, Shan Zhang, Haowen Shi, Hui Chen, Hong Cheng, Lihua Zhou, Chenju Yi, Jiachuan Wang","doi":"10.1093/stcltm/szag070","DOIUrl":"10.1093/stcltm/szag070","url":null,"abstract":"<p><p>Early cortical differentiation in human brain organoids is a critical step of corticogenesis, but remains poorly coordinated under conventional culture conditions. In a standard orbital shaker system, mechanical shear and variability in extracellular matrix support, can disrupt neuroepithelial organisation, leading to inconsistent early cortical differentiation. Here, we investigated how ClinoStar-associated low-shear culture conditions affect early corticogenic marker expression in brain organoids and examined GFRA1/RET-related signaling as a candidate pathway associated with these culture-related effects. Using a low-shear ClinoStar bioreactor, we observed improved neuroepithelial-like expansion, enhanced tissue organisation, and promoted early cortical differentiation during the neuroepithelial expansion stage. Compared with conventional conditions, low-mechanical shear in ClinoStar was associated with increased proliferation capacity and supported the number of TBR2+ intermediate progenitors and TBR1+ early cortical neurons. Transcriptomic analysis revealed enrichment of neuronal differentiation and neuroactive ligand-receptor interaction pathways, with increased upregulation of GDNF signalling components under reduced mechanical shear. Functional experiments showed that GDNF supplementation increased TBR2+ intermediate progenitor-associated and TBR1+ early neuronal marker-related populations in brain organoids, suggesting a positive effect on early corticogenic marker expression. Consistent with this, GFRA1/RET levels were elevated in organoids in the ClinoStar culture with low-mechanical shear stress, and manipulation of GFRA1 affected early cortical differentiation outcomes. These findings suggest that ClinoStar low-shear culture promoted early corticogenic marker expression, potentially associated with GDNF-GFRA1/RET signalling. Collectively, this study provides a refined culture framework for improving the reproducibility and structural organisation of human brain organoid models of early cortical differentiation.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"15 9","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13553076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148913670","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
Why retracted articles can have an influential afterlife-and what to do about it. 为什么撤回的文章会对后世产生影响,该怎么办?
IF 5.9 2区 医学
Stem Cells Translational Medicine Pub Date : 2026-08-18 DOI: 10.1093/stcltm/szag080
Jeremy Snyder, Leigh Turner
{"title":"Why retracted articles can have an influential afterlife-and what to do about it.","authors":"Jeremy Snyder, Leigh Turner","doi":"10.1093/stcltm/szag080","DOIUrl":"10.1093/stcltm/szag080","url":null,"abstract":"<p><p>Retractions of published journal articles are an increasingly common means by which the research community ensures the quality and integrity of publications and addresses research misconduct missed during pre-publication peer review. Retractions are intended to notify the public of issues that undermine the integrity of these publications so that readers will not rely on their findings and conclusions. Continued citation and other uses of these publications without acknowledging their retracted status are therefore problematic and suggest shortcomings in retraction processes. In this commentary, we use the examples of retracted articles published in this journal to outline ways in which retracted articles can maintain an influential afterlife in the academic literature, online materials from non-profit organizations and private businesses, and responses from generative artificial intelligence. Given that this ongoing influence compounds the harms of these publications, we recommend changes in how publishers manage article retractions. These changes include ensuring that article retraction notices are maintained when journal publishing agreements change, increasing the visibility of retractions, and notifying scholars and members of the public when an article they reference is retracted. While these changes will make article retractions more effective, there is a continued need to limit the publication of studies that violate the requirements of research integrity.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"15 9","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13549933/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148906973","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
MSCs derived from ADSC-reprogrammed iPSCs exhibit enhanced therapeutic potential for treating skin fibrosis. 来自adsc重编程iPSCs的MSCs在治疗皮肤纤维化方面表现出增强的治疗潜力。
IF 5.9 2区 医学
Stem Cells Translational Medicine Pub Date : 2026-08-18 DOI: 10.1093/stcltm/szag063
Liquan Wang, Mingfei Lu, Meili Zhang, Lin Kang, Fengzhou Du, Nanze Yu, Jiuzuo Huang, Yue Huang, Xiao Long
{"title":"MSCs derived from ADSC-reprogrammed iPSCs exhibit enhanced therapeutic potential for treating skin fibrosis.","authors":"Liquan Wang, Mingfei Lu, Meili Zhang, Lin Kang, Fengzhou Du, Nanze Yu, Jiuzuo Huang, Yue Huang, Xiao Long","doi":"10.1093/stcltm/szag063","DOIUrl":"10.1093/stcltm/szag063","url":null,"abstract":"<p><strong>Background: </strong>Localized scleroderma (LoS) is a fibrotic skin disorder characterized by excessive collagen deposition, leading to functional and cosmetic impairments. Mesenchymal stromal cells (MSCs) offer therapeutic potential through immunomodulation and tissue repair, but their clinical use is limited by donor variability and replicative senescence. Induced pluripotent stem cell (iPSC)-derived MSCs (iMSCs) present a promising alternative owing to their scalable production and rejuvenated phenotype.</p><p><strong>Methods: </strong>We generated adipose-derived iMSCs (AD-iMSCs) from reprogrammed adipose-derived stem cells (ADSCs) and compared their therapeutic efficacy to primary ADSCs in vitro and in vivo. Functional assays including transcriptomic profiling, conditioned medium (CM) effects on fibrosis markers (α-SMA, TGF-β/Smad), and angiogenesis were conducted. A bleomycin-induced murine LoS model was employed to assess AD-iMSC engraftment, collagen deposition, and microvascularization.</p><p><strong>Results: </strong>AD-iMSCs exhibited rejuvenated-like phenotype, with reduced senescence markers and enhanced proliferative capacity. AD-iMSC-derived conditioned medium (AD-iMSCs-CM) outperformed ADSC-derived conditioned medium (ADSC-CM) in promoting angiogenesis in vitro. In vivo, AD-iMSCs demonstrated superior persistence and therapeutic efficacy, notably decreasing dermal thickness and collagen density while promoting vascularization. Mechanistically, AD-iMSCs more effectively suppressed the TGF-β/Smad2/3 signaling and extracellular matrix (ECM) remodeling pathways compared to ADSCs.</p><p><strong>Conclusion: </strong>In conclusion, our findings provide a robust preliminary proof-of-concept demonstrating that iPSC-mediated reprogramming yields iMSCs with rejuvenated-like phenotype and a potent anti-fibrotic secretome. These data offer a valuable molecular and functional rationale for the prospective development of iMSC-based platforms to circumvent the expansion limitations and donor variability inherent to primary MSC therapies for fibrotic skin disorders.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"15 9","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13533559/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148875735","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
Temporal mapping of radiation-induced neural injury and mitigation in human cortical organoids. 人类皮质类器官辐射诱导的神经损伤及其缓解的时间图谱。
IF 5.9 2区 医学
Stem Cells Translational Medicine Pub Date : 2026-08-18 DOI: 10.1093/stcltm/szag071
Ling He, Harley I Kornblum, Aparna Bhaduri, Frank Pajonk
{"title":"Temporal mapping of radiation-induced neural injury and mitigation in human cortical organoids.","authors":"Ling He, Harley I Kornblum, Aparna Bhaduri, Frank Pajonk","doi":"10.1093/stcltm/szag071","DOIUrl":"10.1093/stcltm/szag071","url":null,"abstract":"<p><strong>Background: </strong>Radiation therapy is a standard-of-care oncological treatment for central nervous system (CNS) malignancies. However, as survival outcomes improve, radiation-induced injury to normal brain tissue has increased in clinical significance. CNS radiation injury is a delayed, multifactorial process characterized by impaired neurogenesis, reactive gliosis, and persistent functional deficits. Mechanistic exploration and development of effective radiation mitigators have been limited by the lack of scalable, human-relevant models.</p><p><strong>Methods: </strong>Mature human iPSC-derived cortical organoids were exposed to single-dose or clinically relevant fractionated radiation (5 × 2 Gy). DNA damage, apoptosis, and growth dynamics were assessed longitudinally. Structural organization, synaptic integrity, and neuroinflammatory responses were evaluated by immunofluorescence and real-time PCR. Transcriptomic profiling was performed at 72 hours and 2 weeks after fractionated radiation to capture acute and delayed effects. Two candidate radiation mitigators, NSPP and amisulpride, were tested for their therapeutic effects within the organoid system.</p><p><strong>Results: </strong>Cortical organoids exhibited partial recovery following single doses up to 4 Gy or fractioned irradiation. Transcriptomic analyses revealed that radiation not only reduced overall cell viability but also reshaped lineage trajectories, characterized by depletion of neural stem/progenitor populations, loss of neuronal identity, enhanced gliogenesis, increased inflammatory cytokines, and disrupted cortical layering and synaptic integrity. Treatment with NSPP or amisulpride attenuated injury-associated transcriptional and structural alterations.</p><p><strong>Conclusion: </strong>Human cortical organoids recapitulate key features of radiation-induced neural injury, recovery, and therapeutic modulation, providing a robust, scalable, and human-relevant platform for studying CNS radiation biology and preclinical screening of candidate radiation mitigators.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"15 9","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13529364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148866106","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
M1-primed human corneal stromal stem cell-derived exosomes delivering protein-coding transforming growth factor-β3 RNA promote corneal regeneration. m1引发的人角膜基质干细胞来源的外泌体传递蛋白质编码转化生长因子-β3 RNA促进角膜再生。
IF 5.9 2区 医学
Stem Cells Translational Medicine Pub Date : 2026-08-18 DOI: 10.1093/stcltm/szag079
Mithun Santra, Elizabeth Rubin, Syeda R Ali, Moira L Geary, Christine Chandran, Julia T Coelho, Ella J Dewald, Xi Cheng, Martha L Funderburgh, Deepinder K Dhaliwal, Xin D Gao, Vishal Jhanji, Gary H F Yam
{"title":"M1-primed human corneal stromal stem cell-derived exosomes delivering protein-coding transforming growth factor-β3 RNA promote corneal regeneration.","authors":"Mithun Santra, Elizabeth Rubin, Syeda R Ali, Moira L Geary, Christine Chandran, Julia T Coelho, Ella J Dewald, Xi Cheng, Martha L Funderburgh, Deepinder K Dhaliwal, Xin D Gao, Vishal Jhanji, Gary H F Yam","doi":"10.1093/stcltm/szag079","DOIUrl":"10.1093/stcltm/szag079","url":null,"abstract":"<p><strong>Introduction: </strong>Human corneal stromal stem cells (hCSSCs), which exhibit mesenchymal stem cell (MSC) features, prevent fibrotic scarring and promote regeneration of injured stromal tissue, thereby restoring corneal clarity in mice. These therapeutic effects rely on hCSSCs' ability to respond to early inflammatory cues, suppress chronic neutrophil infiltration, and inhibit fibrosis. In this study, we examined the responses of hCSSCs to transient pro-inflammatory M1 stimulation and characterized the exosomes (Exo) they secreted.</p><p><strong>Methods: </strong>We evaluated the expression of full-length protein-coding human TGFB3 mRNA molecules in purified Exo, and investigated Exo uptake, induction of human transforming growth factor β3 (hTGFβ3) protein expression, and the effects of different hTGFβ3/β1 ratios on myofibroblast generation from human corneal stromal keratocytes (CSKs) and stromal fibroblasts (SFs). The anti-scarring effect of hCSSC-Exo enriched in TGFB3 mRNA was assessed in a mouse model of acute corneal stromal injury.</p><p><strong>Results: </strong>Our results showed that hCSSC-Exo contained TGFB3 mRNA transcripts, and their abundance increased following pro-inflammatory M1 stimulation. Exo uptake enhanced hTGFβ3 protein expression in hCSKs, and a higher hTGFβ3/β1 ratio in hCSKs and hSFs suppressed expression of α-smooth muscle actin and TGFβ1-induced myofibroblast differentiation. In vivo, topical treatment with M1-primed hCSSC-Exo reduced corneal opacity compared with sham-treated controls. Notably, hCSSC-Exo enriched with TGFB3 mRNA demonstrated greater scar-reducing and wound-healing efficacy.</p><p><strong>Conclusions: </strong>M1-primed hCSSC-Exo containing protein-coding TGFB3 mRNA significantly inhibited corneal opacity and promoted scar-free healing in injured mouse corneas. These findings support the anti-fibrotic and regenerative potential of hCSSC-Exo, which can be developed as a cell-free therapeutic strategy for corneal fibrosis and scarring.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"15 9","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13543683/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148892407","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
Serum-induced recovery of proliferative capacity and differentiation potential in aged dental pulp stem cells. 血清诱导衰老牙髓干细胞增殖能力和分化潜能的恢复。
IF 5.9 2区 医学
Stem Cells Translational Medicine Pub Date : 2026-08-18 DOI: 10.1093/stcltm/szag072
Cho-Yeon Park, Joung-Ho Moon, Sang-Man Lee, Eun-Hye Lee, Joo-Young Park, Sun-Young Kim
{"title":"Serum-induced recovery of proliferative capacity and differentiation potential in aged dental pulp stem cells.","authors":"Cho-Yeon Park, Joung-Ho Moon, Sang-Man Lee, Eun-Hye Lee, Joo-Young Park, Sun-Young Kim","doi":"10.1093/stcltm/szag072","DOIUrl":"10.1093/stcltm/szag072","url":null,"abstract":"<p><strong>Background: </strong>Aging impairs the proliferative, survival, and differentiation capacities of dental pulp stem cells (DPSCs), thereby limiting their regenerative potential. This study systematically investigated whether high-serum preconditioning could promote serum-induced recovery of age-associated functional decline in rat and human DPSCs.</p><p><strong>Methods: </strong>Young, older, and high-serum-conditioned DPSCs were compared using in vitro assays assessing proliferation, survival, colony-forming efficiency, and multilineage differentiation, together with in vivo functional regeneration models and transcriptomic profiling of human DPSCs.</p><p><strong>Results: </strong>High-serum preconditioning significantly enhanced proliferation and colony-forming efficiency in older DPSCs and restored osteogenesis and neurogenesis through serum-induced recovery, approaching the levels of young cells. In vivo, transplantation of high-serum-conditioned DPSCs resulted in organized axonal regeneration accompanied by compact myelin formation, as well as improved bone regeneration in calvarial defect models, demonstrating functional recovery beyond in vitro outcomes. Human DPSCs cultured under high-serum conditions similarly exhibited increased proliferation, viability, and lineage-specific differentiation capacity while maintaining stable expression of mesenchymal stem cell markers. Transcriptomic analysis revealed extensive remodeling under high-serum conditions, including activation of stemness- and cell cycle-related gene programs and suppression of senescence-associated transcripts. However, global gene expression patterns indicated only partial convergence toward a youthful transcriptional state rather than complete rejuvenation.</p><p><strong>Conclusions: </strong>High-serum preconditioning promotes serum-induced recovery and partially restores the regenerative competence of older DPSCs through reconfiguration of functional and molecular programs without full reversion to a youthful state. This study provides preliminary insight into serum-induced recovery and a framework for identifying serum-derived factors for future stem cell-based regenerative applications.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"15 9","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13505630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148819493","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
Stem cell-based therapeutics in epilepsy: current advances and future prospects. 干细胞治疗癫痫:当前进展和未来前景。
IF 5.9 2区 医学
Stem Cells Translational Medicine Pub Date : 2026-08-18 DOI: 10.1093/stcltm/szag077
Napasiri Putthanbut, Jea-Young Lee, Cesario V Borlongan
{"title":"Stem cell-based therapeutics in epilepsy: current advances and future prospects.","authors":"Napasiri Putthanbut, Jea-Young Lee, Cesario V Borlongan","doi":"10.1093/stcltm/szag077","DOIUrl":"10.1093/stcltm/szag077","url":null,"abstract":"<p><p>Epilepsy represents as one of the most prevalent and serious neurological disorders, with approximately one-third of patients resistant to conventional treatments. Current pharmacologic therapies primarily suppress seizures without targeting the underlying epileptogenesis, resulting in unchanged long-term prognosis. At the same time, epilepsy surgery remains underutilized due to the requirement for extensive evaluations and specialized expertise. Stem cell-based therapy has emerged as a promising avenue, offering the potential to address both the neurological and neuropsychiatric aspects. This review summarizes recent preclinical and clinical studies on stem cell therapy in epilepsy, with a focus on their mechanisms of action, including direct engraftment, restoration of normal neurogenesis, and immunomodulation via bystander effect. Advances in genetic engineering, extracellular vesicle-based therapy, and patient-derived brain organoids offer more personalized treatment strategies. Although stem cell therapy holds significant promise as a treatment for epilepsy, further extensive research is required to establish its clinical safety and efficacy.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"15 9","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13544966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148892371","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
Lysine methyltransferase methyltransferase-like 13 regulates bone marrow mesenchymal stem cells osteo-adipogenic differentiation and senescence in osteoporosis via the Foxa1/HES-1 axis. 赖氨酸甲基转移酶甲基转移酶样13通过Foxa1/HES-1轴调控骨质疏松症中骨髓间充质干细胞的成骨脂肪分化和衰老。
IF 5.9 2区 医学
Stem Cells Translational Medicine Pub Date : 2026-07-20 DOI: 10.1093/stcltm/szag049
Ying Liu, Ao Wang, Ziwen Liu, Zhengwei Qin, Lei Yin, Xinyue Wang, Mingyu He, Tao Li, Yanquan Wang, Longhao Chen, Zhuo Liu, Jiayi Liu, Binsha Gu, Shichao Yang, Hui Liang, Yang Li, Xiaofei Zheng, Shuixing Zhang, Baofeng Yang, Ye Yuan, Lei Yang
{"title":"Lysine methyltransferase methyltransferase-like 13 regulates bone marrow mesenchymal stem cells osteo-adipogenic differentiation and senescence in osteoporosis via the Foxa1/HES-1 axis.","authors":"Ying Liu, Ao Wang, Ziwen Liu, Zhengwei Qin, Lei Yin, Xinyue Wang, Mingyu He, Tao Li, Yanquan Wang, Longhao Chen, Zhuo Liu, Jiayi Liu, Binsha Gu, Shichao Yang, Hui Liang, Yang Li, Xiaofei Zheng, Shuixing Zhang, Baofeng Yang, Ye Yuan, Lei Yang","doi":"10.1093/stcltm/szag049","DOIUrl":"10.1093/stcltm/szag049","url":null,"abstract":"<p><strong>Purpose: </strong>Recent research indicates that the senescence of bone marrow mesenchymal stem cells (BMSCs) disrupts the osteo-adipogenic balance, a primary factor contributing to the development of osteoporosis. Our previous findings have implicated methyltransferases in this process, among which methyltransferase-like 13 (METTL13) has been established to regulate cell fate, although its role in osteoporosis has yet to be determined.</p><p><strong>Methods: </strong>Bone formation was assessed using micro-computed tomography and hematoxylin and eosin staining. Protein expression in bone tissues was examined immunohistochemically, and cellular mRNA and protein levels were determined using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting. Cellular senescence was evaluated based on β-galactosidase staining, and osteogenic and adipogenic differentiation was examined using alkaline phosphatase, Alizarin Red S, and Oil Red O staining. Protein interactions and DNA binding were determined using co-immunoprecipitation and chromatin immunoprecipitation.</p><p><strong>Results: </strong>METTL13 expression was significantly enhanced in ovariectomy-induced senescent bone and BMSCs, whereas METTL13 knockdown markedly reversed etoposide-induced cellular senescence. By binding to forkhead box protein A1 (Foxa1), METTL13 promotes the preferential differentiation of BMSCs into adipocytes, as opposed to osteocytes. Moreover, Foxa1 had effects opposite to those of METTL13 on BMSC differentiation, inhibiting the nuclear entry of METTL13. Notably, blocking the nuclear import of Foxa1 suppressed the transcriptional expression of HES-1, which promoted the adipogenic differentiation of BMSCs and inhibited osteogenic differentiation.</p><p><strong>Conclusions: </strong>Our findings in this study revealed the mechanisms whereby METTL13 promotes BMSC senescence and disrupts BMSC differentiation, on the basis of which, we identified the METTL13-Foxa1-HES-1 axis as a potential therapeutic target for treatment of osteoporosis.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"15 8","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13415456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148607555","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
Red blood cell differentiation using canine-induced pluripotent stem cells. 利用犬诱导的多能干细胞分化红细胞。
IF 5.9 2区 医学
Stem Cells Translational Medicine Pub Date : 2026-07-20 DOI: 10.1093/stcltm/szag058
Kazuto Kimura, Masaya Tsukamoto, Kohei Shishida, Hiroko Sugisaki, Jun Katahira, Miyuu Tanaka, Mitsuru Kuwamura, Amir Kol, Mika Okada, Minoru Iijima, Mahito Nakanishi, Kikuya Sugiura, Shingo Hatoya
{"title":"Red blood cell differentiation using canine-induced pluripotent stem cells.","authors":"Kazuto Kimura, Masaya Tsukamoto, Kohei Shishida, Hiroko Sugisaki, Jun Katahira, Miyuu Tanaka, Mitsuru Kuwamura, Amir Kol, Mika Okada, Minoru Iijima, Mahito Nakanishi, Kikuya Sugiura, Shingo Hatoya","doi":"10.1093/stcltm/szag058","DOIUrl":"10.1093/stcltm/szag058","url":null,"abstract":"<p><strong>Background: </strong>Red blood cell (RBC) transfusions are essential for treating various medical conditions, but global demand is difficult to meet due to a dwindling donor pool and compatibility issues. Pluripotent stem cells (PSCs) offer a promising alternative of blood dependent on volunteer donors for RBC production, and dogs serve as an excellent model for translational research due to their physiological and genetic similarities to humans.</p><p><strong>Methods: </strong>Canine induced pluripotent stem cells (ciPSCs) were differentiated toward hematopoietic and erythroid lineages. Differentiated cells were evaluated for hematopoietic marker expression, hemoglobinization, colony-forming capacity, enucleation, and hemoglobin gene expression. Glycophorin A (GYPA)-enhanced green fluorescent protein (EGFP) reporter ciPSC lines were generated using clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9-mediated genome editing to visualize GYPA expression during differentiation.</p><p><strong>Results: </strong>This study introduces a protocol for RBC differentiation using ciPSCs. We achieved generation of hemoglobinized RBCs, progressing through polychromatic and orthochromatic erythroblast-like stages. CiPSC-derived hematopoietic cells/RBCs were confirmed to have immature characteristics as determined by limited colony-forming capacities, low enucleation, and embryonic and fetal hemoglobin gene expression. Additionally, we created GYPA-EGFP reporter ciPSC lines using CRISPR-Cas9-mediated genome editing, enabling real-time visualization of GYPA expression. This innovation confirmed GYPA as a viable surface marker for ciPSC-derived RBCs.</p><p><strong>Conclusion: </strong>Our findings mark an initial step toward establishing a canine PSC-based erythroid differentiation system, providing a foundation for future improvements and exploration of applications for canine PSC-derived RBCs.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"15 8","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13381058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148520995","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
Correction to: The global regulatory landscape of stem cell medical aesthetics: challenges, comparisons, and pathways to coordination. 修正:干细胞医学美学的全球监管格局:挑战、比较和协调途径。
IF 5.9 2区 医学
Stem Cells Translational Medicine Pub Date : 2026-07-20 DOI: 10.1093/stcltm/szag066
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