Cell Regeneration最新文献

{"title":"Efficacy of neonatal mouse muscle extracellular vesicles in skeletal muscle repair and regeneration.","authors":"Chengwei Liu, Zhouyan Li, Xinyue Liu, Sitong Lv, Xijun Yin","doi":"10.1186/s13619-025-00274-6","DOIUrl":"10.1186/s13619-025-00274-6","url":null,"abstract":"<p><p>Currently, effective treatments for skeletal muscle injury remain limited. The self-repair of skeletal muscle relies on the activation and differentiation of satellite cells (SCs), which fuse with damaged myofibers to form new fibers and thereby support muscle regeneration. However, in cases of severe injury, it is difficult for muscle tissue to fully restore its original structure and function, and its regenerative capacity is often markedly reduced. Thus, there is an urgent need to develop therapies that enhance muscle repair and restore physiological function. In this study, we investigated extracellular vesicles derived from neonatal mouse skeletal muscle (NMM-EVs), which are enriched in cargo from Pax7⁺ myogenic progenitor cells. We hypothesized that NMM-EVs could enhance SC activation and improve muscle regeneration following injury. Using glycerol-induced tibialis anterior (TA) muscle injury model, we evaluated the effects of intramuscular NMM-EV administration on skeletal muscle regeneration by histological, immunofluorescence, and functional analyses. In vivo, NMM-EVs significantly promoted skeletal muscle regeneration and functional recovery, upregulated Pax7 expression, increased the cross-sectional area and muscle mass of regenerated TA, and reduced fibrosis and fat infiltration. In vitro, NMM-EVs enhanced the proliferation and myogenic differentiation of mouse SCs and increased the expression of myogenic regulatory factors at both the mRNA and protein levels. In conclusion, this study demonstrates that NMM-EVs activate SCs within injured muscle, promote their proliferation and differentiation, and thereby accelerate injury repair and myofiber regeneration while attenuating fibrotic and adipogenic remodeling. These findings provide a scientific basis for the development of neonatal muscle-derived extracellular vesicle-based, cell-free therapeutic strategies for skeletal muscle injury.</p>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":"15 1","pages":"6"},"PeriodicalIF":4.7,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12827838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146028366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LncRNA nonnmmut065573 promotes post-myocardial infarction cardiac fibrosis and activates the TGF-β1/ZEB1 pathway.","authors":"Chaowei Hu, Lijie Han, Zhiyong Du, Huahui Yu, Yunhui Du, Linyi Li, Haili Sun, Yu Wang, Xiaoqian Gao, Xuechun Sun, Zihan Zhang, Lanqing Liu, Yanjing Zhang, Yanwen Qin","doi":"10.1186/s13619-025-00275-5","DOIUrl":"10.1186/s13619-025-00275-5","url":null,"abstract":"<p><p>Cardiac fibrosis following myocardial infarction (MI) is a critical determinant of progressive cardiac dysfunction, yet the underlying mechanisms driving this pathological process remain incompletely understood. Elucidating these regulatory pathways holds profound implications for improving post-MI prognosis.Our prior work demonstrated that chronic intermittent hypoxia (CIH) exacerbates cardiac fibrosis while modulating the expression of long non-coding RNA (lncRNA) nonnmmut065573 (tentatively designated LncRNA-IH) in cardiac tissues. Herein, we sought to determine the role of LncRNA-IH in post-MI cardiac fibrosis and its underlying mechanisms. Using a C57BL/6 mouse model of MI, we established a mouse model with cardiac-specific overexpression of LncRNA-IH to evaluate post-MI cardiac fibrosis. In vitro, primary cardiac fibroblasts (MCF) and the PA12 cell line were subjected to LncRNA-IH overexpression or siRNA-mediated knockdown, and cell proliferation and migration were assessed. Transcriptomic profiling was performed to characterize LncRNA-IH-induced changes in cardiac gene expression and signaling pathways, aiming to elucidate the molecular mechanisms involved.Results showed that CIH significantly exacerbated post-MI cardiac fibrosis, and LncRNA-IH was predominantly localized to cardiac fibroblasts. Cardiac-specific overexpression of LncRNA-IH in MI mice markedly exacerbated post-MI cardiac dysfunction and fibrosis. In vitro, LncRNA-IH overexpression significantly enhanced the proliferation and migration capacities of primary cardiac fibroblasts and PA12 cells, whereas these effects were abrogated by LncRNA-IH knockdown. Transcriptomic analysis revealed that LncRNA-IH elicited significant alterations in cardiac gene expression profiles, specifically activating the TGF-β1 signaling pathway and upregulating the expression of its downstream target, ZEB1.Collectively, our findings indicate that LncRNA-IH promotes cardiac fibroblast proliferation and migration, thereby exacerbating post-MI cardiac remodeling, at least in part through activation of the TGF-β1 signaling pathway. This study identifies LncRNA-IH as a potential therapeutic target for mitigating post-MI cardiac fibrosis and preserving cardiac function.</p>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":"15 1","pages":"5"},"PeriodicalIF":4.7,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12824076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146008682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transient inhibition of MEK/ERK and WNT pathways enhances direct differentiation of primed hPSCs into functional trophoblast stem cells.","authors":"Qifan Jiang, Ping Liu, Chunlin Chen","doi":"10.1186/s13619-025-00261-x","DOIUrl":"10.1186/s13619-025-00261-x","url":null,"abstract":"<p><p>The placenta plays a pivotal role in human pregnancy, yet research into placental development has been hindered by limited access to early-stage embryos and ethical constraints. Although human trophoblast stem cells (hTSCs) have been established from blastocysts, deriving these cells efficiently from primed human pluripotent stem cells (hPSCs) remains challenging. Here, we developed a simplified and efficient strategy that enables direct, efficient conversion of primed hPSCs into stable, self-renewing hTSCs by transiently inhibiting the MEK/ERK signaling pathway using the inhibitor PD0325901 in a simplified basal medium. This approach significantly enhanced the generation of trophoblast cells expressing the critical trophoblast marker GATA3 and led to the establishment of homogeneous hTSC lines with robust capacities to differentiate into functional extravillous trophoblast (EVT) and syncytiotrophoblast (STB) lineages. Transcriptomic and chromatin accessibility analyses confirmed that these hTSCs closely resembled blastocyst-derived trophoblast cells and clearly differed from amnion lineages, confirming authentic trophoblast identity distinct from amnion. Additionally, precise modulation of WNT signaling activity was essential for optimal trophoblast induction efficiency, highlighting the importance of signaling equilibrium in trophoblast differentiation. Collectively, our optimized protocol offers an accessible and reproducible platform for modeling early placental development and understanding the pathogenesis of trophoblast-associated disorders in vitro.</p>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":"15 1","pages":"4"},"PeriodicalIF":4.7,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12816472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146003069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Endogenous retroviral ERVH48-1 promotes human urine cell reprogramming.","authors":"Yuling Peng, Jieying Zhu, Qi Zhang, Ran Zhang, Zhenhua Wang, Zesen Ye, Ning Ma, Dajiang Qin, Duanqing Pei, Dongwei Li","doi":"10.1186/s13619-026-00281-1","DOIUrl":"10.1186/s13619-026-00281-1","url":null,"abstract":"","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":"15 1","pages":"3"},"PeriodicalIF":4.7,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12816481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145997312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of a chemical small molecule inducing umbilical cord mesenchymal stem cell differentiation to vascular endothelial cells.","authors":"Bangzhao Zhou, Xiaohui Chi, Xinyu Xie, Baoxiang Zhao, Li Wang, Junying Miao, Zhaomin Lin","doi":"10.1186/s13619-025-00278-2","DOIUrl":"10.1186/s13619-025-00278-2","url":null,"abstract":"<p><p>Human umbilical cord mesenchymal stem cells (hUC-MSCs) have emerged as promising candidates for clinical applications in vascular disease therapy and in the in vitro modeling of vascular regeneration. However, the translational potential of hUC-MSCs requires direct differentiation into functional vascular lineage cells, particularly vascular endothelial cells (VECs) and endothelial progenitor cells (EPCs). A critical challenge is the lack of reliable sources that yield sufficient quantities of mature VECs/EPCs for therapeutic purposes. To address this limitation, we established an efficient protocol for generating VECs from hUC-MSCs. Preconditioning hUC-MSCs using small molecules with cytoprotective properties can enhance their potential for use in cell-based therapeutics. Through systematic screening, we identified CPP as a novel small chemical molecule that effectively induces the endothelial differentiation of hUC-MSCs. Remarkably, our CPP-based induction protocol achieved > 90% conversion to functionally competent VECs within 5 days, as evidenced by both in vitro assays and in vivo functional validation. Single-cell RNA sequencing (scRNA-seq) analysis further delineated the differentiation trajectory and confirmed the acquisition of endothelial-specific molecular signatures during lineage commitment. These findings establish CPP as a potent inducer of rapid endothelial differentiation, and provide mechanistic insights into stem cell fate determination.</p>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":"15 1","pages":"2"},"PeriodicalIF":4.7,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12811175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145988429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mammalian mesenchymal stromal cells enhance zebrafish fin regeneration.","authors":"Dora Sapède, Claudia Terraza-Aguirre, Jholy De La Cruz, Claire Vinatier, Jérôme Guicheux, Christian Jorgensen, Farida Djouad","doi":"10.1186/s13619-025-00273-7","DOIUrl":"10.1186/s13619-025-00273-7","url":null,"abstract":"<p><p>Mesenchymal stromal cells (MSCs) possess well-described immunoregulatory properties, yet their capacity to drive regeneration in vertebrates is still debated and their mechanisms of action remain to be fully elucidated. In this study, we used zebrafish larvae, a highly regenerative vertebrate model to study the effects of MSC delivery on caudal fin fold regeneration and monitored macrophage dynamics through live imaging in fluorescent reporter lines. We found that MSCs enhanced fin regeneration by increasing the early recruitment of inflammatory (tnfa +) macrophages at 1-day-post-amputation (dpA), and accelerating resolution between 2 and 3 dpA. Given the established role of prostaglandin E2 (PGE2) in MSC-mediated immunoregulation, we examined its contribution using indomethacin, a cyclooxygenase inhibitor that suppresses PGE2 production in grafted MSCs. We observed that PGE2 inhibition abolished the pro-regenerative effect of MSCs and maintained elevated tnfa + macrophage levels. PGE2-inhibited MSCs were more susceptible to phagocytosis by both zebrafish and mammalian macrophages, while maintaining viability, indicating a loss of PGE2-mediated protection in treated cells. Together, these findings demonstrate that MSC-derived PGE2 is essential for MSC regenerative function by promoting MSC persistence and modulating macrophage behavior, highlight the zebrafish as a powerful in vivo platform to dissect stem cell-immune interactions and optimize MSC-based regenerative strategies.</p>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":"15 1","pages":"1"},"PeriodicalIF":4.7,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12808003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145984396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alpha-ketoglutarate promotes random-pattern skin flap survival by enhancing angiogenesis via PI3K/Akt/HIF-1α signaling pathway.","authors":"Jiefeng Huang, Shuangmeng Jia, Yitong Ji, Yingjia Zhu, Yishu Lu, Yiming Tang, Jiajie Yang, Guangpeng Liu, Lei Cui, Shuaijun Li","doi":"10.1186/s13619-025-00264-8","DOIUrl":"10.1186/s13619-025-00264-8","url":null,"abstract":"<p><p>Random-pattern skin flaps are widely employed in tissue reconstruction, however, their survival is frequently hindered by ischemia, leading to necrosis. Metabolic alterations have been implicated in playing critical roles in angiogenesis during tissue repair. Using RNA sequencing analysis in a mouse model, we identified significant disruptions in glutamine metabolism, which substantially impaired angiogenesis within random-pattern skin flaps. Although local glutamine repletion failed to alleviate ischemia, administering α-ketoglutarate (α-KG) markedly promoted angiogenesis, as evidenced at both gene and protein levels. In human umbilical vein endothelial cells,α-KG enhanced the stability of hypoxia-inducible factor (HIF-1) alpha through activation of the phosphoinositide 3-kinase (PI3K)-Akt signaling pathway. Notably, α-KG treatment improved flap viability by augmenting blood perfusion, an effect correlated with upregulation of vascular endothelial growth factor expression. Together, these results reveal a novel mechanism by which α-KG enhances random-pattern skin flap viability via promoting angiogenesis through the PI3K/Akt/HIF-1α pathway, offering promising therapeutic insights for improving flap survival.</p>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":"14 1","pages":"54"},"PeriodicalIF":4.7,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12722632/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145803266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"When imaging technology meets single-cell omics: new paradigm in developmental biology.","authors":"Chunling Wang, Xuejing Zhang, Yifan Zhang, Feng Liu","doi":"10.1186/s13619-025-00276-4","DOIUrl":"10.1186/s13619-025-00276-4","url":null,"abstract":"<p><p>Advanced imaging and single-cell omics technologies are fundamentally transforming developmental biology research, shifting it from static observation to dynamic, spatially resolved systems biology. Super-resolution microscopy breaks the diffraction barrier to visualize nanoscale subcellular dynamics, while light-sheet fluorescence microscopy enables long-term, multi-scale volumetric imaging of living specimens. In parallel, single-cell omics (e.g., transcriptomics and proteomics) decipher molecular heterogeneity and lineage trajectories, and spatially resolved transcriptomics maps gene expression within native tissue contexts at subcellular resolution. However, each approach has inherent limitations: imaging lacks deep molecular profiling, while dissociation-based omics loses spatial context. This review highlights how the integration of these technologies bridges cellular behaviors with molecular mechanisms, providing unprecedented multi-scale perspectives on key developmental processes-including embryogenesis, organogenesis, neural patterning, and disease progression. By synergistically capturing the \"when,\" \"where,\" and \"how\" of developmental processes, this convergence resolves longstanding questions and establishes a new mechanistic and predictive paradigm in developmental biology.</p>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":"14 1","pages":"53"},"PeriodicalIF":4.7,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12712248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145767246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A metabolic switch for myelination.","authors":"Shenghui Niu, Lin Zhao, Da Jia","doi":"10.1186/s13619-025-00277-3","DOIUrl":"10.1186/s13619-025-00277-3","url":null,"abstract":"","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":"14 1","pages":"52"},"PeriodicalIF":4.7,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12705893/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145755394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regenerative teeth induced by in vitro mesenchymal cells in mice via repressing BMP4 and activating retinoic acid/osteopontin.","authors":"Shubin Chen, Yifan Zhao, Hongxing Chu, Qinxing Mo, Jiashu Zhang, Xiaoming Chen, Yanmei Zhang, Xiaomei Li, Di Wu, Pengfei Liu, Bo Feng, Dajiang Qin, Yaofeng Wang, Duanqing Pei, Jinglei Cai","doi":"10.1186/s13619-025-00271-9","DOIUrl":"10.1186/s13619-025-00271-9","url":null,"abstract":"<p><p>Maintaining the odontogenic potential of dental mesenchymal cells (DMCs) in vitro remains a critical challenge in tooth regeneration research. Current culture systems fail to sustain DMC functionality beyond short-term periods, limiting their utility for tissue engineering applications. Here, we developed an optimized N2B27-based culture medium that preserves the odontogenic capacity of mouse DMCs (mDMCs) for up to 14 days with passaging-a significant improvement over conventional methods (≤ 24 h). Single-cell RNA sequencing (scRNA-seq) revealed distinct transcriptional profiles and cellular trajectories between traditionally cultured (FBS-based) and N2B27-cultured DMCs. Mechanistically, excessive BMP4 signaling in standard media suppressed odontogenesis, whereas elevated Spp1 (osteopontin, OPN) expression in the N2B27 system enhanced regenerative potential. We demonstrate that optimal maintenance of DMC functionality requires balanced BMP4 activity and is enhanced by high OPN levels. Notably, supplementation with recombinant OPN or all-trans retinoic acid (ATRA) partially restored tooth-forming capacity in suboptimal cultures. Our findings establish a robust in vitro platform for DMC expansion while preserving odontogenic competence, advancing both mechanistic studies of tooth development and the generation of clinically relevant cell sources for bioengineered dental tissues. This work provides key insights on the features of a regenerative tooth germ and its odontogenic microenvironment for future translational applications in tooth regeneration.</p>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":"14 1","pages":"51"},"PeriodicalIF":4.7,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12678684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145676605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}