Stem Cell Reviews and Reports最新文献

{"title":"iPSC-Derived 3D Brain Organoids as Next-generation Platforms to Study Viral and Toxicant-associated Neurodegeneration.","authors":"Md Shahadab, Vaishali Saini, Siddharth Singh, Om Prakash, Kumar Sachin, Rajan Kumar Pandey, Ajay Kumar Meena, Hem Chandra Jha","doi":"10.1007/s12015-026-11147-z","DOIUrl":"10.1007/s12015-026-11147-z","url":null,"abstract":"<p><p>Neurodegenerative diseases (ND) are one of the most fatal diseases that affect the majority of individuals worldwide, among which Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common. In vitro 2D monolayer cell cultures and in vivo transgenic animal models have been the primary tools for investigating mechanisms of neurodegenerative diseases. However, the ineffectiveness of these models in translating outcomes into human pathophysiology, necessitates innovative approaches to bridge the translational gap. In this review, we focus on the intricate pathogenic processes by which environmental toxicants and viral infections trigger neurodegeneration. The growing significance of three-dimensional (3D) brain organoids (BOs) derived from induced pluripotent stem cells (iPSCs) can be used as a groundbreaking platform for examining neurodegenerative pathways induced by exposure to environmental toxicants and viral infections. It also addressed how BO's overcomes the fundamental limitations of traditional models, such as 2D cultures and animal models, thereby creating novel opportunities for the mechanistic study of multifactorial neurodegeneration and the development of therapeutic interventions.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"2380-2393"},"PeriodicalIF":4.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147875604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Accessory Inner Segment-Like Structures Develop in Human Retinal Organoids.","authors":"Kristen E Ashworth, Cassandra D'Amata, Brian G Ballios","doi":"10.1007/s12015-026-11144-2","DOIUrl":"10.1007/s12015-026-11144-2","url":null,"abstract":"<p><strong>Purpose: </strong>A novel photoreceptor structure, called the accessory inner segment (aIS), was recently identified in human rod photoreceptors. It is described as a microtubule-based, mitochondria-rich extension of the conventional inner segment attached externally to the outer segment. Human retinal organoids recapitulate many developmental and mature cellular features of the human retina. Thus, we sought to determine if retinal organoids exhibit an aIS-like structure, to support future in vitro studies of its role in photoreceptor structure and disease.</p><p><strong>Methods: </strong>Mature retinal organoids were derived from human induced pluripotent stem cells and displayed stratified photoreceptor layers with inner- and outer segment-like processes. Immunohistochemistry and confocal imaging were used to identify aIS-like projections extending from inner segments. Electron microscopy (EM) was used to evaluate these structures in both transverse and longitudinal orientations.</p><p><strong>Results: </strong>Co-staining of β-tubulin with ATP synthase revealed examples of discrete microtubule- and mitochondria-rich projections, respectively, emerging apically from the inner segments of mature organoids, consistent with previously-described aIS morphology observed in cadaveric human retina. β-tubulin and GPR98 co-staining further supported the presence of aIS-associated projections, spatially distinct from the outer segment axonemes, extending from the inner segment. Transmission EM confirmed examples of aIS-like structures enriched with microtubules and mitochondria, positioned apposed to the presumptive outer segment.</p><p><strong>Conclusion: </strong>Here, we provide the first evidence that aIS-like structures, previously observed only in cadaveric human retina, can be recapitulated in human retinal organoids. These findings may enable future in vitro investigations of photoreceptor structure to uncover new vulnerabilities relevant to retinal degenerations.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"2603-2611"},"PeriodicalIF":4.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147857289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial Regulation of Periodontal Ligament Stem Cell Fate and Function.","authors":"Zixuan Zhao, Sijia Liu, Na Liu, Qing Liu","doi":"10.1007/s12015-026-11148-y","DOIUrl":"10.1007/s12015-026-11148-y","url":null,"abstract":"<p><p>Periodontal ligament stem cells (PDLSCs) are regarded as among the most promising seed cells for periodontal tissue regeneration because of their strong self-renewal ability, multipotent differentiation potential, and accessibility. However, their biological behaviors vary significantly under different microenvironments and stimuli, and the underlying regulatory mechanisms remain unclear. Recent advances have identified mitochondria as central signaling hubs that regulate cell fate. This review summarizes current progress in understanding the role of mitochondria in modulating the biological behaviors of PDLSCs, focusing on mitochondrial reactive oxygen species and oxidative stress, mitochondrial dynamics, mitophagy, glucose metabolic reprogramming, and tricarboxylic acid cycle metabolites. We integrate evidence linking mitochondrial function with key biological processes in PDLSCs, including osteogenic differentiation, senescence, inflammation, apoptosis, and regenerative capacity. Furthermore, we highlight major unresolved issues and challenges in current research and emphasize the significant \"dual effects\" of mitochondria-related signaling in diverse physiological and pathological conditions. A deeper understanding of mitochondrial regulatory networks in PDLSCs may provide a theoretical foundation for mitochondria-targeted precision therapies and reveal novel therapeutic strategies for periodontal tissue regeneration and related diseases.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"2334-2354"},"PeriodicalIF":4.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Priming of Mesenchymal Stem Cells for Tendon Regeneration: Mechanisms and Clinical Translation.","authors":"Ki-Bong Park, Hasung Park, Young Dae Jeon","doi":"10.1007/s12015-026-11146-0","DOIUrl":"10.1007/s12015-026-11146-0","url":null,"abstract":"<p><p>Rotator cuff tears remain a major cause of shoulder dysfunction; however, retears and incomplete healing persist despite advances in surgical repair. Conventional techniques fail to restore the native tendon-bone interface, resulting in mechanically inferior scar tissue. Mesenchymal stem cell (MSC)-based augmentation has emerged as a promising biological strategy. However, naïve MSCs exhibit limited survival and integration in the hypoxic and inflammatory microenvironments of degenerative tendons. Recent advances in MSC priming using cytokines, hypoxia, and mechanical conditioning have enhanced angiogenesis, immunomodulation, and tenogenic differentiation. Primed MSCs and their extracellular vesicles facilitated organised collagen architecture and fibrocartilage formation and enhanced biomechanical competence at the repair interface, resulting in earlier mechanical stability and more durable tendon healing. The remaining challenges include the standardisation of priming protocols, scalable manufacturing, and validation of potency assays. This review synthesises emerging evidence on MSC priming for tendon regeneration, crucially assesses its histological and biomechanical foundations, and elucidates its translational potential for achieving biologically integrated and clinically durable rotator cuff repair.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"2371-2379"},"PeriodicalIF":4.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147869412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reimagining Regeneration: How Human Amniotic Fluid Stem Cells Derived Extracellular Vesicles Address Vascular and Bladder Pathology in Diabetes.","authors":"Prakash Gangadaran, Ramya Lakshmi Rajendran, Byeong-Cheol Ahn","doi":"10.1007/s12015-026-11139-z","DOIUrl":"10.1007/s12015-026-11139-z","url":null,"abstract":"","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"2632-2635"},"PeriodicalIF":4.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Priming-Dependent Modulation of Secretome in Placenta- and Adipose-Derived Mesenchymal Stromal/Stem Cells: Toward Cell-Free Immunoregenerative Therapies for Osteochondral and Degenerative Joint Diseases.","authors":"Mattia Emanuela Ligotti, Elisabetta Scalia, Simone Dario Scilabra, Margot Lo Pinto, Alessia Gallo, Roberta Vazzana, Nicola Cuscino, Oriana Lo Re, Clara Pipia, Giandomenico Amico, Silvia Lopa, Alessandra Colombini, Viviana Ippolito, Antonio Maurizi, Nadia Rucci, Valentina Agnese, Pier Giulio Conaldi, Matteo Moretti, Vitale Miceli, Matteo Bulati","doi":"10.1007/s12015-026-11122-8","DOIUrl":"10.1007/s12015-026-11122-8","url":null,"abstract":"<p><p>Age-related joint diseases are driven by structural deterioration, chronic inflammation, and impaired regenerative capacity. Mesenchymal stromal/stem cells (MSCs) have emerged as promising therapeutic candidates due to their immunomodulatory and regenerative effects, largely mediated by their secretome and extracellular vesicles (EVs). However, the therapeutic efficacy of MSC-derived products depends on both the cell source and the conditioning stimuli to which MSCs are exposed. In this study, we characterized secretomes derived from placenta-derived MSCs (PDSCs) and adipose-derived MSCs (ASCs) by performing a comparative proteomic and exosomal microRNA (miRNA) profiling. Moreover, the impact of different priming strategies, including hypoxia, interferon-gamma (IFNγ), and interleukin-1 beta (IL1β), on the paracrine properties of these cells was assessed.Proteomic analysis identified over 7,000 proteins, with PDSC secretome enriched in pathways related to osteogenesis, chondrogenesis, extracellular matrix organization, angiogenesis, and immune regulation, whereas ASC secretome displayed limited enrichment in these processes. Functional scoring highlighted IL1β priming as the most effective strategy to enhance osteochondral and immunomodulatory protein signatures in PDSCs. Differently, IFNγ priming selectively expanded the repertoire of exosomal miRNAs, with enrichment in signalling networks including Wnt/β-catenin, TGF-β, NF-κB, and T cell receptor pathways, underscoring its role in fine-tuning immune and regenerative functions.Together, our findings revealed that PDSCs secrete a broader and more functionally relevant spectrum of bioactive molecules for osteochondral applications compared with ASCs. Moreover, distinct priming strategies showed to differentially regulate cell paracrine outputs. In particular, while IL1β primarily enhances protein-driven regenerative and immunomodulatory activity, IFNγ promotes a functionally enriched exosomal miRNA cargo. These results indicate PDSC-derived secretomes as versatile candidates for next-generation, cell-free therapies in joint diseases.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"2453-2473"},"PeriodicalIF":4.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13241456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147730081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thrombopoietin Receptor MPL in Hematopoiesis and Myeloproliferative Neoplasms: Physiological Roles and Pathogenic Mechanisms.","authors":"Shujing Zhang, Muhammad Sameer Ashaq, Miaomiao Xu, Meiqi Guo, Lingling Wang, Zhuoran Li, Yi Wang, Yufeng Huang, Yuan Li, Baobing Zhao","doi":"10.1007/s12015-026-11136-2","DOIUrl":"10.1007/s12015-026-11136-2","url":null,"abstract":"<p><p>MPL (myeloproliferative leukemia virus) is a type I transmembrane glycoprotein acting as the receptor for thrombopoietin (TPO). Increasing evidence indicates that MPL is essential for stem cell maintenance and megakaryopoiesis. Activating mutations in MPL have been identified as the major driver mutations of myeloproliferative neoplasms (MPNs) characterized by excessive proliferation of multiple lineages. Given its dual role in hematopoiesis and MPN pathogenesis, studies of MPL reveal the imbalance between stem cell homeostasis and malignant proliferation. Here, we summarize MPL’s physiological functions and pathogenic roles, with the aim to provide novel insights into disease mechanisms and potential therapeutic strategies.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"2252-2265"},"PeriodicalIF":4.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Omentum-Derived Mesenchymal Stem Cells Promote Antibacterial Effects and Protect Endothelial Functions via PAI-1.","authors":"Adeline Castro Ramos, Cat-Khanh Vuong, Mizuho Fukushige, Yuri Ushijima, Kazuya Morikawa, Motoo Osaka, Chiho Tokunaga, Yuji Hiramatsu, Osamu Ohneda","doi":"10.1007/s12015-026-11152-2","DOIUrl":"10.1007/s12015-026-11152-2","url":null,"abstract":"","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"2655"},"PeriodicalIF":4.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13241439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147875573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization and Validation of Long-Term Cultured TERT-Immortalized Human Wharton's Jelly-Derived Mesenchymal Stromal Cells.","authors":"Young Eun Kim, So Yoon Ahn, Yeon Ju Lee, Sein Hwang, Yun Sil Chang","doi":"10.1007/s12015-026-11118-4","DOIUrl":"10.1007/s12015-026-11118-4","url":null,"abstract":"<p><p>Mesenchymal stromal cells (MSCs) have demonstrated efficacy and feasibility in numerous preclinical and clinical studies. However, their application is limited at early passages owing to replicative senescence. This study investigated whether MSCs immortalized via human telomerase reverse transcriptase (TERT) overexpression (TERT-MSCs) maintain their characteristics and efficacy after extended passaging. Human Wharton’s jelly-derived MSCs at passage (P) 6 were immortalized by retroviral transfection with human TERT. TERT-MSCs at mid (P13) and late (P30) passages were analyzed. Their morphology, differentiation potential, and surface marker expression were preserved throughout extended passaging. Single-cell RNA sequencing reconfirmed the characteristics of TERT-MSCs and compared their gene expression profiles with those of P8 parental (control) cells. As passage number increased, control MSCs exhibited gradual declines in TERT expression, telomere length, and cytoprotective effects, whereas both P13 and P30 TERT-MSCs retained these properties. Expression levels of paracrine-related genes and enriched Gene Ontology terms in extended-passage TERT-MSCs were comparable to those of control MSCs. These findings suggest that TERT-MSCs maintain the key characteristics and therapeutic potential of early-passage MSCs through extended culture, offering a promising approach to overcome the limitations of early-passage MSCs in clinical applications.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"2394-2404"},"PeriodicalIF":4.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13241437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147663268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activation of Bulge Stem Cells through Mechano-Stimulation and ECM Remodeling: Emerging Paradigms in Hair Follicle Regeneration.","authors":"Rinky Kapoor, Mamata Mishra, Debraj Shome, Debalina Bose, Riya Shahare, Raji Patil","doi":"10.1007/s12015-026-11130-8","DOIUrl":"10.1007/s12015-026-11130-8","url":null,"abstract":"","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"2628-2631"},"PeriodicalIF":4.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147730126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}