Cell RegenerationPub Date : 2025-09-28DOI: 10.1186/s13619-025-00257-7
Lixia Zheng, Yuanyuan Chen, Jing-Wei Xiong
{"title":"Rewiring cell identity and metabolism to drive cardiomyocyte proliferation.","authors":"Lixia Zheng, Yuanyuan Chen, Jing-Wei Xiong","doi":"10.1186/s13619-025-00257-7","DOIUrl":"10.1186/s13619-025-00257-7","url":null,"abstract":"<p><p>The adult mammalian heart exhibits minimal regenerative capacity due to postnatal cell-cycle arrest of cardiomyocytes. In contrast, lower vertebrates such as zebrafish retain the ability to fully regenerate heart after injury. This capacity is driven not only by transcriptional and structural plasticity but also by metabolic reprogramming that supports cardiomyocyte proliferation. Adult mammalian cardiomyocytes lack both features, remaining largely refractory to regenerative cues. These limitations have prompted efforts to identify extrinsic genetic and metabolic regulators capable of reactivating proliferative competence in adult cardiomyocytes. In this review, we highlight recent advances in the molecular and metabolic control of cardiomyocyte cell-cycle reentry, focusing on strategies that modulate dedifferentiation, proliferation, and redifferentiation as well as metabolic state transitions. We also examine emerging translational approaches in swine models, which more closely recapitulate human cardiac physiology than rodents. Together, these insights provide a roadmap for unlocking endogenous regenerative pathways and identify key challenges in translating these findings into therapies for heart failure.</p>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":"14 1","pages":"40"},"PeriodicalIF":4.7,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12477098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184604","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":"Drug-induced regeneration of pancreatic beta cells: An approach to cellular therapeutic targets.","authors":"Parinaz Parsi, Saber Saharkhiz, Marzieh Ramezani Farani, Salar Bakhtiyari, Iraj Alipourfard","doi":"10.1186/s13619-025-00255-9","DOIUrl":"10.1186/s13619-025-00255-9","url":null,"abstract":"<p><p>Diabetes mellitus is a common and serious metabolic disease globally, characterized by increased blood glucose levels. The major pathogenesis is the functional impairment of insulin-producing beta cells in the pancreas and the lack of insulin secretion. Although both type 1 and type 2 diabetes develop through distinct pathological mechanisms, they lead to the destruction and/or dysfunction of beta cells, resulting in inadequate beta cell mass to maintain normal blood glucose levels. For this reason, therapeutic agents capable of inducing beta cell proliferation can be considered a possible approach to restore beta cell abundance and treat type 1 and type 2 diabetes. Although several methods have been found to promote the replication of beta cells in animal models or cell lines, it is still challenging to promote the effective proliferation of beta cells in humans. This review highlights the different agents and mechanisms that facilitate pancreatic beta cell regeneration. Numerous small molecules have been discovered to influence beta cell proliferation, primarily by targeting cellular pathways such as DYRK1A, adenosine kinase, SIK, and glucokinase. Additionally, receptors for TGF-β, EGF, insulin, glucagon, GLP-1, SGLT2 inhibitors, and prolactin play critical roles in this process. Stem cell-based clinical trials are also underway to assess the safety and efficacy of stem cell therapies for patients with type 1 and type 2 diabetes. We have emphasized alternative therapeutic pathways and related strategies that may be employed to promote the regeneration of pancreatic beta cells. The knowledge raised within this review may help to understand the potential drug-inducible targets for beta cell regeneration and pave the way for further investigations.</p>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":"14 1","pages":"39"},"PeriodicalIF":4.7,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12413367/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145005962","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}
Cell RegenerationPub Date : 2025-09-05DOI: 10.1186/s13619-025-00260-y
Chang-Ping Li, Ying-Ying Wang, Ching-Wei Zhou, Chen-Yun Ding, Peng Teng, Rui Nie, Shu-Guang Yang
{"title":"Cutting-edge technologies in neural regeneration.","authors":"Chang-Ping Li, Ying-Ying Wang, Ching-Wei Zhou, Chen-Yun Ding, Peng Teng, Rui Nie, Shu-Guang Yang","doi":"10.1186/s13619-025-00260-y","DOIUrl":"10.1186/s13619-025-00260-y","url":null,"abstract":"<p><p>Neural regeneration stands at the forefront of neuroscience, aiming to repair and restore function to damaged neural tissues, particularly within the central nervous system (CNS), where regenerative capacity is inherently limited. However, recent breakthroughs in biotechnology, especially the revolutions in genetic engineering, materials science, multi-omics, and imaging, have promoted the development of neural regeneration. This review highlights the latest cutting-edge technologies driving progress in the field, including optogenetics, chemogenetics, three-dimensional (3D) culture models, gene editing, single-cell sequencing, and 3D imaging. Prospectively, the advancements in artificial intelligence (AI), high-throughput in vivo screening, and brain-computer interface (BCI) technologies promise to accelerate discoveries in neural regeneration further, paving the way for more precise, efficient, and personalized therapeutic strategies. The convergence of these multidisciplinary approaches holds immense potential for developing transformative treatments for neural injuries and neurological disorders, ultimately improving functional recovery.</p>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":"14 1","pages":"38"},"PeriodicalIF":4.7,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12413387/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999723","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}
Cell RegenerationPub Date : 2025-09-04DOI: 10.1186/s13619-025-00259-5
Xiu Yu, Jichang Wang
{"title":"Transgene-free mouse embryo models from chemical reprogramming reach early organogenesis.","authors":"Xiu Yu, Jichang Wang","doi":"10.1186/s13619-025-00259-5","DOIUrl":"10.1186/s13619-025-00259-5","url":null,"abstract":"<p><p>Embryo models derived from pluripotent stem cells (PSCs) have become powerful tools for dissecting mammalian embryonic development and advancing regenerative medicine. Two recent studies in Cell and Cell Stem Cell report major advances in generating mouse embryo models that replicate development up to early organogenesis (equivalent to embryonic day 8.5~8.75). Li et al. describe a purely chemical strategy to reprogram mouse embryonic stem cells (mESCs) into induced embryo founder cells (iEFCs) capable of forming complete embryo models (iEFC-EMs). In parallel, Yilmaz et al. demonstrate transgene-free generation of post-gastrulation models (TF-SEMs) from naive mESCs and induced pluripotent stem cells (iPSCs) using a similar chemical cocktail. Both models faithfully recapitulate key developmental events, including gastrulation, neural tube formation, cardiogenesis, and somitogenesis. These advances not only deepen understanding of early mammalian development but also pave the way for applications in regenerative medicine and disease modeling.</p>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":"14 1","pages":"37"},"PeriodicalIF":4.7,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12411326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991622","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}
Cell RegenerationPub Date : 2025-08-13DOI: 10.1186/s13619-025-00253-x
Ming Shi, Yazhou Sun, Lu Ding, Xinyue Li, Qi Xu, Fuxin Wei, Tianshun Gao, David Y B Deng
{"title":"Integrative analysis and experimental validation identify the role of CD44 and Nucleolin in regulating gliogenesis following spinal cord injury.","authors":"Ming Shi, Yazhou Sun, Lu Ding, Xinyue Li, Qi Xu, Fuxin Wei, Tianshun Gao, David Y B Deng","doi":"10.1186/s13619-025-00253-x","DOIUrl":"10.1186/s13619-025-00253-x","url":null,"abstract":"<p><p>Spinal cord injury (SCI) triggers a complex cascade of cellular and molecular responses, yet the complex cellular communication remains incompletely understood. This study explored how intercellular communication contributes to the activation of microglia and astrocytes after SCI. Here, we integrated four datasets using single-cell RNA sequencing (scRNA-seq) or single-nucleus RNA sequencing (snRNA-seq) and constructed a comprehensive cellular atlas of the injured spinal cord. Transcriptomic changes in microglia and astrocytes were analyzed. We identified CD44 as a key receptor in SPP1-mediated microglial activation, which represented a subpopulation involved in inflammatory response in microglia. We defined a gliogenesis subpopulation of astrocytes that emerged at 3 dpi, which became the predominant cell type in the injured spinal cord. These astrocytes highly expressed the Nucleolin (Ncl) gene and interacted via the Pleiotrophin (Ptn) signaling pathway, which is associated with astrocyte proliferation. To validate these findings, we utilized a crush injury model. Flow cytometry of isolated microglia and astrocytes confirmed the upregulation of CD44 in microglia and NCL in astrocytes in response to SCI. In vivo results confirmed that the CD44 positive microglia accumulated and PLA results further confirmed the combination of SPP1 with CD44. In parallel, the upregulated expression of NCL in astrocytes facilitated their proliferation, underscoring the role of the NCL receptor in gliogenesis after SCI. In vitro validation demonstrated that exogenous SPP1 upregulates CD44 expression by promoting the phosphorylation of p65 and activating the NF-κB pathways in BV2 microglia, and that high expression of IL-6 indicates the activation of inflammation. PTN may enhance NCL expression and thus facilitates astrocyte proliferation. Collectively, our study identified key receptors that regulated inflammation responses and gliogenesis. Targeting the CD44 and NCL receptors may provide promising therapeutic strategies to modulate inflammation and promote tissue repair after SCI.</p>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":"14 1","pages":"35"},"PeriodicalIF":4.7,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12344060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144834254","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}
Cell RegenerationPub Date : 2025-08-12DOI: 10.1186/s13619-025-00256-8
Yaoqi Huang, Haifeng Ye
{"title":"Female germline stem cells: recent advances, opportunities, and challenges to overcome.","authors":"Yaoqi Huang, Haifeng Ye","doi":"10.1186/s13619-025-00256-8","DOIUrl":"10.1186/s13619-025-00256-8","url":null,"abstract":"<p><p>In the field of reproductive medicine, delaying ovarian aging and preserving fertility in cancer patients have long been core issues and relentless pursuits. Female germline stem cells (FGSCs) have been shown to repair aging or damaged ovarian structures and to restore ovarian reproductive and endocrine function. With their unlimited proliferation and directed differentiation into oocytes, FGSCs bring new hope to patients with ovarian insufficiency, malignant tumors, and others needing fertility preservation. In this review, we introduce the role of FGSCs in ovarian fertility preservation and regenerative repair, emphasizing the regulatory pathways of FGSCs in restoring ovarian function. We discuss the unique advantages of FGSCs in infertility treatment, including fertility preservation, animal gene editing, and regenerative medicine. This article aims to offer new research insights for advancing the clinical translation of FGSCs by exploring them from multiple perspectives, such as origin, regulation, and application.</p>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":"14 1","pages":"34"},"PeriodicalIF":4.7,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12343424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144820689","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}
Cell RegenerationPub Date : 2025-07-31DOI: 10.1186/s13619-025-00249-7
Yi Sui, Ziqi Zhou, Siqi Zhang, Zhigang Cai
{"title":"The comprehensive progress of tooth regeneration from the tooth development to tissue engineering and clinical application.","authors":"Yi Sui, Ziqi Zhou, Siqi Zhang, Zhigang Cai","doi":"10.1186/s13619-025-00249-7","DOIUrl":"10.1186/s13619-025-00249-7","url":null,"abstract":"<p><p>The advancement of tooth regeneration has offered revolutionary progress in the treatment of tooth defects and tooth loss, particularly in whole-tooth regeneration, pulp-dentin regeneration, and enamel regeneration. This review comprehensively analyzes the latest research progress in the biological foundations of tooth regeneration, stem cell applications, and tissue engineering technologies while discussing the prospects for clinical translation of these technologies. At present, pulp-dentin regeneration technology has entered clinical trials and demonstrated preliminary efficacy; however, the maturity and controllability of this technology require further enhancement. In situ whole-tooth regeneration has been achieved in animal models but still confronts ethical and functional challenges. Although the development of new materials has provided novel strategies for the epitaxial growth of enamel, enamel regeneration remains in its early stages. Tissue engineering technologies offer new avenues for tooth regeneration but still need to address issues such as immune rejection and long-term stability to realize the clinical application of tooth regeneration technologies.</p>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":"14 1","pages":"33"},"PeriodicalIF":4.7,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12314179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752534","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}
Cell RegenerationPub Date : 2025-07-14DOI: 10.1186/s13619-025-00246-w
Shicheng Yu, Jun Li, Zhaofeng Ye, Mengxian Zhang, Xiaohua Guo, Xu Wang, Liansheng Liu, Yalong Wang, Xin Zhou, Wei Fu, Michael Q Zhang, Ye-Guang Chen
{"title":"Identification of a 10-species microbial signature of inflammatory bowel disease by machine learning and external validation.","authors":"Shicheng Yu, Jun Li, Zhaofeng Ye, Mengxian Zhang, Xiaohua Guo, Xu Wang, Liansheng Liu, Yalong Wang, Xin Zhou, Wei Fu, Michael Q Zhang, Ye-Guang Chen","doi":"10.1186/s13619-025-00246-w","DOIUrl":"10.1186/s13619-025-00246-w","url":null,"abstract":"<p><p>Genetic and microbial factors influence inflammatory bowel disease (IBD), prompting our study on non-invasive biomarkers for enhanced diagnostic precision. Using the XGBoost algorithm and variable analysis and the published metadata, we developed the 10-species signature XGBoost classification model (XGB-IBD10). By using distinct species signatures and prior machine and deep learning models and employing standardization methods to ensure comparability between metagenomic and 16S sequencing data, we constructed classification models to assess the XGB-IBD10 precision and effectiveness. XGB-IBD10 achieved a notable accuracy of 0.8722 in testing samples. In addition, we generated metagenomic sequencing data from collected 181 stool samples to validate our findings, and the model reached an accuracy of 0.8066. The model's performance significantly improved when trained on high-quality data from the Chinese population. Furthermore, the microbiome-based model showed promise in predicting active IBD. Overall, this study identifies promising non-invasive biomarkers associated with IBD, which could greatly enhance diagnostic accuracy.</p>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":"14 1","pages":"32"},"PeriodicalIF":4.0,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12259524/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144625473","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}