STEM CELLSPub Date : 2026-01-08DOI: 10.1093/stmcls/sxaf080
Majlinda Lako
{"title":"Shaping the next era of stem cell science: a vision for stem cells journal and its global community.","authors":"Majlinda Lako","doi":"10.1093/stmcls/sxaf080","DOIUrl":"10.1093/stmcls/sxaf080","url":null,"abstract":"","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12782653/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145754968","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}
{"title":"Bovine formative embryonic stem cell plasticity in embryonic and extraembryonic differentiation.","authors":"Yue Su, Ruifeng Zhao, Yifei Fang, Meiao Renxiu, Guangsheng Li, Liangliang Jin, Jiaxi Liu, Zhen Yang, Ningxiao Li, Jiaqi Zhu, Neha Mishra, Deborah Kaback, Siu Pok Yee, Yan Luo, Wenjing Wan, Yiyu Zhao, Xiangyan Wang, Shiyao Han, Peng Xiao, Chuzhao Lei, Jingyue Ellie Duan, Young Tang, Xiuchun Cindy Tian","doi":"10.1093/stmcls/sxaf068","DOIUrl":"10.1093/stmcls/sxaf068","url":null,"abstract":"<p><p>Bovine embryonic stem cells (bESCs) can greatly enhance the understanding of bovine embryonic development and applications for disease-resistance, biomedical, and zoonotic pre-clinical models. However, formative bESCs with distinct morphology and complete differentiation capacity are still unreported. We document here the generation of formative bESCs (bFSCs) which are pluripotent both in vitro and in vivo, and efficiently converted into neural progenitor cells (NPCs) and primordial germ cell-like cells (PGCLCs) by direct differentiation. Transcriptomic analysis reveals these cells exhibited distinct metabolic features from human and mouse ESCs and early embryos. bFSCs contributed to a wide range of cell types within embryonic and extraembryonic tissues after aggregating with mouse and bovine embryos, as confirmed by chimeric experiment and single cell RNA-seq (scRNA-seq). The establishment of bFSCs with dual developmental plasticity represents a milestone for agricultural biotechnology and decoding the underlying mechanism of bona fide bovine pluripotency.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
STEM CELLSPub Date : 2026-01-08DOI: 10.1093/stmcls/sxaf065
Bailey R Klein, Angella Blake, Ritisha Rashmil, Amar B Desai
{"title":"Novel strategies to expand and engineer hematopoietic stem cells.","authors":"Bailey R Klein, Angella Blake, Ritisha Rashmil, Amar B Desai","doi":"10.1093/stmcls/sxaf065","DOIUrl":"10.1093/stmcls/sxaf065","url":null,"abstract":"<p><p>Hematopoietic stem cell (HSC) transplantation is a lifesaving therapy for hematologic diseases, but its broader application remains constrained by challenges in sourcing, manipulating, and reliably expanding functional HSCs. In this review, we discuss strategies to expand and engineer HSCs by recreating essential aspects of the bone marrow niche. These include defined cytokine cocktails, small molecule modulators, stromal co-culture systems, and biomaterials that promote self-renewal while limiting differentiation. We highlight advances in three-dimensional organoid models and microfluidic platforms that better support long-term repopulating cells and reflect native microenvironments. In parallel, progress in gene delivery platforms, including both viral and nonviral approaches, is enabling more efficient and targeted modification of HSCs for therapeutic use in genetic disorders such as sickle cell disease and β-thalassemia. While these tools have advanced significantly, significant hurdles remain in scaling, preserving stem cell identity, and reducing culture-induced stress. Continued refinement of biomimetic systems and genome engineering technologies will be central to expanding the clinical utility of HSC-based therapies.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145249232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
STEM CELLSPub Date : 2026-01-08DOI: 10.1093/stmcls/sxaf067
Raghavan Chinnadurai, Anant Madabhushi
{"title":"Opportunities with artificial intelligence in assessing the potency of mesenchymal stromal cells.","authors":"Raghavan Chinnadurai, Anant Madabhushi","doi":"10.1093/stmcls/sxaf067","DOIUrl":"10.1093/stmcls/sxaf067","url":null,"abstract":"<p><p>Determining the potency of MSCs is a critical component of their application as cellular therapies. The function of MSCs does not rely on a single mechanism but rather on overlapping and cumulative effector pathways, which necessitates the assay matrix strategy in potency analysis. Artificial intelligence (AI) tools can significantly enhance the assay matrix strategy by generating novel potency scores that capture unified critical quality attributes that may not be readily discernible through human analysis. AI can provide precise potency metrics for investigational MSC products by comparing them to appropriate controls. The next generation of MSC potency analysis will increasingly rely on AI tools, as they can match patients with MSC products exhibiting the most appropriate potency profiles for personalized and targeted therapies. A significant challenge in deploying AI tools is the need for robust predictors of efficacy that relates to the potency of investigational MSC products. Nevertheless, AI has the potential to stratify patients who are most likely to respond to MSC therapy by leveraging clinical data in combination with detailed potency analyses. We discuss these opportunities and challenges in this perspective article.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12790435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145385530","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}
STEM CELLSPub Date : 2026-01-08DOI: 10.1093/stmcls/sxaf066
Thomas W C Knight, Ngefor Asangwe, Sadia Mohsin, Mohsin Khan
{"title":"Decoding developmental signaling for heart regeneration.","authors":"Thomas W C Knight, Ngefor Asangwe, Sadia Mohsin, Mohsin Khan","doi":"10.1093/stmcls/sxaf066","DOIUrl":"10.1093/stmcls/sxaf066","url":null,"abstract":"<p><p>The adult heart consists of a fixed number of cardiomyocytes (CMs) determined at birth. CMs once lost due to injury in the adult heart are never replaced, initiating a viscous cycle of adverse events leading to heart failure. Therapeutic interventions that drive cardiac repair by proliferation of the endogenous CMs or adoptive transfer of stem cells such as cardiac tissue derived stem/progenitor cells (CPCs) are promising albeit limited in their ability to repair the heart. Numerous studies have identified an inherent regenerative power of the heart during embryonic and postnatal development. The developmental cardiac tissue can initiate a robust regenerative response leading to complete resolution of injury. Unique cellular and molecular mechanisms in the developmental heart are at the core of this regenerative ability. Upon cardiac maturation, cellular differentiation and changes in molecular signaling hubs active developmentally are 'switched off' in the adult heart. Recent work has shown convincing results for promoting cardiac repair in the adult heart by reactivation of developmental signaling. CPCs engineering with developmental factors or their CMs specific delivery of can reactivate regenerative signaling to augment cardiac structure and function in the adult heart. This review aims to summarize efforts regarding reactivation of developmental signaling factors in the heart using CPCs and CMs. A special emphasis is on embryonic/developmental microRNAs governed signaling pathways for cardiac repair. We provide an in-depth analysis of the current state of the field including discussion of some of the limitations that will be beneficial for future studies.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145278601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
STEM CELLSPub Date : 2026-01-08DOI: 10.1093/stmcls/sxaf063
Xianqi Wang, Dan Wu, Xiaoyang Liu, Yanan Xu, Peiwen Wang, Heliang Fu, Yuexiang Ma, Shanshou Liu, Qianmei Wang, Xian-Jie Xu, Zheng Dai, Qi Zhang, Wen Yin, Kuo Shen, Junjie Li
{"title":"Exosomes derived from ADSC suppress endothelial cells ferroptosis and alleviate sepsis acute liver injury via regulation of Keap1/Nrf2/GPX4 axis.","authors":"Xianqi Wang, Dan Wu, Xiaoyang Liu, Yanan Xu, Peiwen Wang, Heliang Fu, Yuexiang Ma, Shanshou Liu, Qianmei Wang, Xian-Jie Xu, Zheng Dai, Qi Zhang, Wen Yin, Kuo Shen, Junjie Li","doi":"10.1093/stmcls/sxaf063","DOIUrl":"10.1093/stmcls/sxaf063","url":null,"abstract":"<p><strong>Background: </strong>Adipose-derived stem cell exosome (ADSC-exo) has been reported to be effective in alleviating organ dysfunction in sepsis, including acute liver injury (ALI). Whether ADSC-exo protects the liver via suppression of vascular endothelial cell (VEC) ferroptosis is unclear.</p><p><strong>Methods: </strong>We evaluated the viability and migration of VECs and their ferroptosis-related indices. To further elucidate this mechanism, we examined the Nrf2/GPX4 pathway. Cecal ligation and puncture (CLP) was performed to establish a sepsis model to observe the protective effect of ADSC-exo. The death rate and liver tissue injury were observed. We also evaluated inflammation- and ferroptosis-related indices. Next, we examined the expression of nuclear factor erythroid 2-related factor 2 (Nrf2)/glutathione peroxidase 4 (GPX4) pathway-related molecules to elucidate the underlying mechanism.</p><p><strong>Results: </strong>ADSC-exo reduced cell injury and ferroptosis in VECs. ADSC-exo increased the expression and nuclear translocation of Nrf2. In the CLP-induced sepsis model, ADSC-exo relieved liver injury and reduced the death rate. Further observations showed that ADSC-exo significantly alleviated oxidative stress injury and ferroptosis in liver tissue, while remarkably increasing the expression of Nrf2 and GPX4.</p><p><strong>Conclusions: </strong>These findings demonstrate the remarkable ability of ADSC-exo to alleviate sepsis-induced ALI by mitigating endothelial cell ferroptosis, providing evidence for the potential clinical application of ADSC-exo in ALI therapy.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
STEM CELLSPub Date : 2025-11-17DOI: 10.1093/stmcls/sxaf070
Laura Hansen, Cecilie Mullerup Laustsen-Kiel, Filip Rangatchew, Charlotte Harken Jensen, Ditte Caroline Andersen, Rikke Holmgaard
{"title":"Mesenchymal stromal cell therapy for scarring: a systematic review of clinical and preclinical studies.","authors":"Laura Hansen, Cecilie Mullerup Laustsen-Kiel, Filip Rangatchew, Charlotte Harken Jensen, Ditte Caroline Andersen, Rikke Holmgaard","doi":"10.1093/stmcls/sxaf070","DOIUrl":"10.1093/stmcls/sxaf070","url":null,"abstract":"<p><strong>Background: </strong>Mesenchymal stromal/stem cell (MSC) transplantation has emerged as a promising therapeutic strategy for managing cutaneous scarring, an issue associated with significant aesthetic and functional morbidity. This systematic review evaluates the potential of MSCs to modulate scarring, highlighting their efficacy and distinct mechanisms from traditional scar treatments.</p><p><strong>Materials and methods: </strong>The review adheres to the PRISMA guidelines. We followed a prospectively registered protocol and conducted comprehensive searches in the PubMed and EMBASE databases. Eleven studies, including preclinical and clinical trials, met the inclusion criteria. Study quality was assessed using the ROBINS-I and Cochrane Risk of Bias 2 tools.</p><p><strong>Discussion: </strong>MSC and MSC-conditioned medium therapies derived from adipose tissue, bone marrow, or the umbilical cord demonstrated significant improvements in scar appearance, reductions in thickness and volume, and beneficial remodeling of collagen structures. MSC treatment positively influenced inflammatory and immunomodulatory responses, as reflected by the regulation of cytokines and fibrotic biomarkers. However, the heterogeneity in methodologies, MSC sources, and administration routes limits the ability to make conclusive statements. Furthermore, insufficient transparency in MSC preparation challenges clinical reproducibility and application.</p><p><strong>Conclusion: </strong>MSC therapy is becoming increasingly important in regenerative medicine. Based on our findings, MSC therapy demonstrates potential in scar remodeling through antifibrotic and immunomodulatory effects. However, robust randomized controlled trials and standardized product reporting are essential to confirm long-term efficacy and safety, improve reproducibility, and facilitate clinical translation. Advancements in these areas will define the future role of MSC therapies in managing scarring.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145375516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
STEM CELLSPub Date : 2025-11-17DOI: 10.1093/stmcls/sxaf062
Shan Tao, Dongxue Zhuang, Chengqiang Jin
{"title":"Comment on \"critical role of the potential O-linked glycosylation sites of CXCR4 in cell migration and bone marrow homing of hematopoietic stem progenitor cells\".","authors":"Shan Tao, Dongxue Zhuang, Chengqiang Jin","doi":"10.1093/stmcls/sxaf062","DOIUrl":"10.1093/stmcls/sxaf062","url":null,"abstract":"","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The impact of donor and recipient age on post-transplantation clonality in murine hematopoiesis.","authors":"Lars Thielecke, Kalpana Nattamai, Aishlin Hassan, Ingmar Glauche, Hartmut Geiger, Kerstin Cornils","doi":"10.1093/stmcls/sxaf059","DOIUrl":"10.1093/stmcls/sxaf059","url":null,"abstract":"<p><strong>Introduction: </strong>The sustained production of blood and immune cells is driven by a pool of hematopoietic stem cells (HSCs) and their offspring. Due to the intrinsic heterogeneity of HSCs, the composition of emergent clones changes over time, leading to a reduced clonality in aging mice and humans. Theoretical analyses suggest that clonal conversion rates and clonal complexity depend not only on HSC heterogeneity, but also on additional stress conditions. These insights are particularly relevant in the context of stem cell transplantations, which still remain the only curative option for many hematologic diseases, increasingly considered viable for elderly individuals. However, age-related clonal changes post-transplantation are not well understood.</p><p><strong>Methods: </strong>To address this, we conducted a barcode-based assessment of clonality to investigate post-transplantation changes in both homo- and hetero-chronic settings, combined with low- and high-intensity pre-conditioned recipients.</p><p><strong>Results: </strong>A robust and polyclonal engraftment was observed across all groups, but with distinct differences in barcode diversity. In particular, transplanted aged HSCs showed no changes in clonality, regardless of recipient age or pre-conditioning. Young HSCs transplanted into severely pre-conditioned old hosts as well as under reduced pre-conditioning, allowed for full lymphoid reconstitution, but showed substantial differences in clonality. Also, myeloid lineage bias, a hallmark of aged HSCs, was confirmed at a clonal level across all experimental groups. Overall, we found that aged HSCs generally maintain clonal diversity similar to young HSCs, but notable differences emerge under hetero-chronic conditions and varying pre-conditioning regimens.</p><p><strong>Conclusion: </strong>These findings challenge current paradigms and underscore the complex interactions between aging and transplantation conditions.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12622992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991166","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}