Rinky Kapoor, Varad Rajendra Saptarshi, Raji Patil, Debraj Shome
{"title":"\"Hair Follicle Stem Cells and their Lymphatic Niche: An Overlooked Axis in Cutaneous Regeneration\".","authors":"Rinky Kapoor, Varad Rajendra Saptarshi, Raji Patil, Debraj Shome","doi":"10.1007/s12015-026-11150-4","DOIUrl":"https://doi.org/10.1007/s12015-026-11150-4","url":null,"abstract":"","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147864536","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}
Kristen E Ashworth, Cassandra D'Amata, Brian G Ballios
{"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":"https://doi.org/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":""},"PeriodicalIF":4.2,"publicationDate":"2026-05-09","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":"Exosomal Biomarkers: Paving the Way for Precision Diagnosis in Orthopedics.","authors":"Ramya Lakshmi Rajendran, Prakash Gangadaran, Sathish Muthu, Byeong-Cheol Ahn","doi":"10.1007/s12015-026-11151-3","DOIUrl":"https://doi.org/10.1007/s12015-026-11151-3","url":null,"abstract":"","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843039","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}
Margarida Varela, Minna Ampuja, Martin Broberg, Amanda Ramste, Virpi Talman, Emmi Helle
{"title":"Hypoplastic Left Heart Syndrome Cardiomyocytes Exhibit Intrinsic Stress Vulnerabilities and Augmented Stress Responses in vitro.","authors":"Margarida Varela, Minna Ampuja, Martin Broberg, Amanda Ramste, Virpi Talman, Emmi Helle","doi":"10.1007/s12015-026-11127-3","DOIUrl":"https://doi.org/10.1007/s12015-026-11127-3","url":null,"abstract":"<p><strong>Background: </strong>Hypoplastic left heart syndrome (HLHS) is a severe congenital heart defect characterised by underdevelopment of left-sided cardiac structures. While genetic predisposition contributes to HLHS, the relevance of environmental stressors is increasingly recognised, yet the cellular mechanisms linking genetic susceptibility to environmental vulnerability remain unclear. We aimed to identify molecular and functional differences between cardiomyocytes derived from HLHS patients and healthy controls to uncover potential susceptibilities contributing to the HLHS phenotype.</p><p><strong>Methods: </strong>Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from HLHS patients and healthy controls were used to examine intrinsic cellular differences. Single-cell RNA sequencing compared baseline transcriptional profiles. Functional assays assessed responses to endothelin-1 (ET-1)-induced stress, cyclic mechanical stretch, and basal or mitogen-stimulated proliferation. These approaches were used to identify intrinsic functional impairments and altered stress responses in HLHS cardiomyocytes.</p><p><strong>Results: </strong>Single-cell transcriptomics revealed downregulation of gene networks associated with cardiac stress responses, metabolic resilience, and rhythm regulation in HLHS cardiomyocytes. Regulon analysis revealed broad reductions in transcription factor activity across key cardiac regulatory networks. Functionally, HLHS cardiomyocytes showed heightened vulnerability to ET-1, with exaggerated proBNP induction compared with controls. No significant differences were observed following cyclic mechanical stretch. Basal proliferation varied across HLHS lines, while mitogen-induced proliferation remained comparable to controls.</p><p><strong>Conclusions: </strong>These findings support a model in which intrinsic molecular and functional vulnerabilities in HLHS cardiomyocytes might reduce resilience to developmental stressors. Such gene-environment interactions may contribute to HLHS pathogenesis, underscoring the interplay between genetic predisposition and environmental influences in congenital heart disease.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147842979","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}
Menfild Margotonne, Nicolas Gendron, Olivier Sanchez, Samuel Benarroch, Alexandre G Lellouch, Katharina Rus, Isabelle Mahé, Dominique Helley, David M Smadja
{"title":"Circulating Biomarkers of Vascular Regeneration are not Associated with Residual Pulmonary Vascular Obstruction after Pulmonary Embolism: A Retrospective Observational Biomarker Study.","authors":"Menfild Margotonne, Nicolas Gendron, Olivier Sanchez, Samuel Benarroch, Alexandre G Lellouch, Katharina Rus, Isabelle Mahé, Dominique Helley, David M Smadja","doi":"10.1007/s12015-026-11149-x","DOIUrl":"https://doi.org/10.1007/s12015-026-11149-x","url":null,"abstract":"<p><strong>Background: </strong>Residual pulmonary vascular obstruction (RPVO) persists in a substantial proportion of patients after acute pulmonary embolism (PE) despite adequate anticoagulation and is associated with long-term functional impairment. Angiogenesis plays a central role in thrombus resolution and vascular repair. In a recent prospective study, lower circulating CD34⁺ cell levels at follow-up were associated with the presence of RPVO, suggesting impaired regenerative and angiogenic capacity in patients with persistent perfusion defects. Whether classical circulating angiogenic biomarkers reflect this process remains unknown.</p><p><strong>Objective: </strong>To assess the relationship between angiogenic marker levels and the presence of RPVO ≥10% after an episode of PE.</p><p><strong>Patients and methods: </strong>This single-center retrospective study included patients diagnosed with acute PE who received at least three months of anticoagulant therapy between January 1999 and June 2006. During the follow-up consultation, performed 6-12 months after PE diagnosis, patients underwent a ventilation/perfusion lung scan, and peripheral blood sampling for plasma biobanking. Angiogenic markers (VEGF-A, FGF-2, PlGF, MMP-1, MMP-8, endoglin, and endostatin) were measured in plasma samples collected at this visit. Levels were compared between patients with a perfusion defect (RPVO ≥10%) and those without (RPVO <10%) on ventilation/perfusion scintigraphy.</p><p><strong>Results: </strong>Among 126 patients evaluated 6 to 12 months after a PE diagnosis, 39 (31%) had RPVO ≥10%. Median levels of VEGF-A, FGF-2, PlGF, MMP-1, MMP-8, endostatin, and endoglin did not significantly differ between patients with RPVO ≥10% and those with RPVO <10%.</p><p><strong>Conclusion: </strong>None of the angiogenic markers measured reflected the perfusion defect observed in patients.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147842964","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":"https://doi.org/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":""},"PeriodicalIF":4.2,"publicationDate":"2026-05-05","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":"Engineering and Integrating Blood Vessel Organoids: a Comprehensive Blueprint for Physiological and Disease Modeling.","authors":"Yanlin Xu, Nuerjiamali Wubuli, Jiaoyue Zhang","doi":"10.1007/s12015-026-11145-1","DOIUrl":"https://doi.org/10.1007/s12015-026-11145-1","url":null,"abstract":"<p><p>The human vascular network is a highly dynamic, complex and organ-specific microenvironment essential for organ homeostasis. Traditional 2D cell cultures fail to capture its complex intercellular interactions, tissue-specific architectures, and mechanobiological cues. Blood vessel organoids (BVOs) generated from human induced pluripotent stem cells (hiPSCs) replicate the structure and function of blood vessels. Because hiPSCs preserve the donor's telomere length and epigenetic memory, BVOs may preserve the genesis memory, opening up a completely new avenue for the study of vascular disorders. In this review, we systematically outline the methods for in vitro blood vessel generation and explore how vascularizing parenchymal organoids actively drives tissue maturation while overcoming hypoxic limitations. We assess the vital transition from biochemical induction to biomechanical integration, highlighting how microfluidic organ-on-a-chip (OoC) platforms resolve the lineage-specific media dilemma and impose the physiological shear stress necessary for definitive vascular maturation. Furthermore, we comprehensively summarize the applications of BVOs as personalized preclinical avatars across diverse pathologies, including diabetic vasculopathy, cerebrovascular and cardiovascular diseases, tumor immune evasion, hereditary anomalies, and infectious vasculotropism. Finally, we address critical current bioengineering constraints-notably incomplete vessel maturation, the absence of functional lymphatic systems, and the lack of immunocompetent microenvironments-providing strategic future perspectives to accelerate the translation of BVOs in precision and regenerative medicine.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147842967","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}
Zhengrui Li, Zhaocheng Pan, Yang Su, Lai Jiang, Débora Brito Goulart, Jinyang Wu, Shilei Zhang
{"title":"YAP Signaling Pathway in Bone Regeneration: Mechanisms, Crosstalk, and Clinical Biomaterial Applications.","authors":"Zhengrui Li, Zhaocheng Pan, Yang Su, Lai Jiang, Débora Brito Goulart, Jinyang Wu, Shilei Zhang","doi":"10.1007/s12015-026-11103-x","DOIUrl":"10.1007/s12015-026-11103-x","url":null,"abstract":"","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"2038-2040"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147514605","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":"Stem Cells in Aging and Anti-Aging.","authors":"Zongke Bai, Zhong Li","doi":"10.1007/s12015-026-11093-w","DOIUrl":"10.1007/s12015-026-11093-w","url":null,"abstract":"","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"1527-1536"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147514631","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}
Mamata Mishra, Akbarsha Mohammad Abdulkader, Rinky Kapoor, Debraj Shome
{"title":"Accelerating New Approach Methodologies (NAMs): The iPSC Revolution in Toxicology and Biomedical Science.","authors":"Mamata Mishra, Akbarsha Mohammad Abdulkader, Rinky Kapoor, Debraj Shome","doi":"10.1007/s12015-026-11112-w","DOIUrl":"10.1007/s12015-026-11112-w","url":null,"abstract":"","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"2045-2049"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147575523","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}