Stem Cell Reviews and Reports最新文献

{"title":"Mesenchymal stem Cells and Extracellular Vesicles in Bladder Dysfunction: Mechanisms and Translational Perspectives.","authors":"Penghui Zhong, Jin Chen, Shijie Cai, Junrong Zou, Xuyang Zhong, Guoxi Zhang","doi":"10.1007/s12015-026-11209-2","DOIUrl":"https://doi.org/10.1007/s12015-026-11209-2","url":null,"abstract":"<p><p>Bladder dysfunction comprises diverse lower urinary tract disorders lacking treatments that restore tissue integrity and neural control. While mesenchymal stem cells (MSCs) show promise in regenerative urology, their benefits primarily stem from paracrine mechanisms. Consequently, MSC-derived extracellular vesicles (MSC-EVs) have emerged as superior cell-free alternatives, recapitulating the parent cells' regenerative potential with enhanced biosafety, stability, and controllability.This review summarizes advances in MSC- and MSC-EV-based therapies for bladder conditions, including neurogenic, diabetic, overactive/underactive bladder, outlet obstruction, and interstitial cystitis. Mechanistically, these therapies exert multi-target effects: modulating immunity, suppressing fibrosis (via TGF-β inhibition), attenuating inflammation (via NF-κB/NLRP3), promoting angiogenesis, and enhancing neuroregeneration. MSC-EVs drive these processes by precisely transferring bioactive microRNAs and proteins.We propose a paradigm shift from conventional cell therapies to MSC-EV-centric, cell-free strategies, which overcome traditional transplantation limitations like low engraftment and immunogenicity. While early data confirm feasibility and safety, challenges in standardizing EV isolation, dosing, and long-term efficacy remain. Ultimately, this review establishes MSC-EVs as a next-generation therapeutic framework, guiding future clinical translation in regenerative urology.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148761199","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":"Oxygen-generating Microparticles Enhance Viability and Functionality of Human Pluripotent Stem Cell-derived Cardiomyocytes for Myocardial Infarction Therapy.","authors":"Xingyu He, Suchandrima Dutta, Darshini Desai, Sheng Zhong, William Liu, Sophie Chen, Wei Huang, Waqas Ahmad, Jialiang Liang, Yigang Wang","doi":"10.1007/s12015-026-11163-z","DOIUrl":"10.1007/s12015-026-11163-z","url":null,"abstract":"<p><strong>Background: </strong>Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) represent a promising therapy for myocardial infarction (MI), but their survival is severely limited by the hypoxic infarct environment. The optimal oxygen levels required to maintain the viability and functionality of hiPSC-CMs remain poorly defined. This study aimed to develop a controlled oxygen-delivery system to support engineered heart tissue (EHT) for cardiac regeneration.</p><p><strong>Methods: </strong>Oxygen-generating particles (OGPs) were engineered using peroxide (sodium percarbonate) and antioxidant (β-carotene (βCAR)) components encapsulated in PLGA microparticles. The effects of OGPs on hiPSC-CMs were evaluated through oxidative stress assays, cell viability analysis, and contractility measurements. RNA-seq was performed to investigate gene expression changes in hiPSC-CMs in response to OGPs and hypoxic stress. hiPSC-CMs combined with OGPs were encapsulated in a 3D hydrogel to generate oxygen-releasing engineered heart tissue (OR-EHT), which was implanted into infarcted hearts of immunodeficient mice. Cardiac function was assessed by echocardiography, and cell engraftment was evaluated using immunostaining.</p><p><strong>Results: </strong>OGPs provided controlled oxygen release for up to 22 days. Inclusion of βCAR minimized OGP-induced oxidative stress, preserved mitochondrial membrane potential, and maintained cell viability. OGP treatment enhanced calcium signaling and contractility in hiPSC-CMs. Transcriptomic analysis revealed that genes associated with CM maturation and contractile function were upregulated following OGP pretreatment. In addition, OGP pretreatment significantly reduced HIF-1α expression, decreased mitochondrial fragmentation, and improved survival. RNA-seq further demonstrated activation of oxygen-responsive metabolic pathways that facilitated cellular adaptation to hypoxic stress. In vivo, OR-EHT implantation for 6 weeks improved cardiac function, increased ejection fraction, reduced ventricular remodeling, and decreased infarct size compared with EHT without OGPs. Moreover, OGP incorporation significantly enhanced engraftment and survival of transplanted hiPSC-CMs and supported features consistent with early structural integration with host myocardium.</p><p><strong>Conclusion: </strong>OGP-mediated oxygen delivery offers a promising strategy for oxidative preconditioning and significantly improves the regenerative efficacy of hiPSC-CM-based cardiac therapies.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"2846-2862"},"PeriodicalIF":4.9,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13354643/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148035317","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":"Clinical Development of Mesenchymal Stem Cells Therapies Worldwide: Current Landscape and Emerging Promises.","authors":"Ran Yin, Xuan Jiang, Suiting Ao, Yufan Zhai, Qing Zhao","doi":"10.1007/s12015-026-11166-w","DOIUrl":"10.1007/s12015-026-11166-w","url":null,"abstract":"","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"2961-2964"},"PeriodicalIF":4.9,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148144794","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":"Type 2 Diabetes-Induced Molecular and Functional Impairment of Adipose Tissue-Derived Mesenchymal Stromal Cells (ASCs) and Interferon Gamma Priming for Enhanced Diabetic ASC-Based Therapy.","authors":"Alaa Zeinhom, Ammar Y Mohamed, Nahla N Abdel-Aziz, Mostafa Sayed Diab, Amir M H Salem, Noha N Yassen, Eman E A Mohammed, Amal M Mohamed, Ola M Eid, Shymaa H Hussein, Marwa Farid, Engy K Tharwat, Kholoud A Ali, Hesham A Elmeligy, Sahar A Fadallah, Osama Azmy, Nourhan Abu-Shahba, Marwa Mahmoud","doi":"10.1007/s12015-026-11164-y","DOIUrl":"10.1007/s12015-026-11164-y","url":null,"abstract":"<p><strong>Background: </strong>Transplantation of adipose-derived mesenchymal stromal cells (ASCs) or their insulin-producing derivatives holds promise for diabetes mellitus therapy due to their regenerative properties. However, the harsh microenvironment in type 2 diabetes (T2D) likely impairs autologous ASC efficacy.</p><p><strong>Aim: </strong>This study investigated transcriptomic alterations and therapeutic efficacy of ASCs from T2D patients (dASCs) in experimental diabetes, compared to healthy donors (ndASCs), and evaluated whether inflammatory priming could enhance dASC functionality.</p><p><strong>Methods: </strong>dASCs and ndASCs were characterized phenotypically and functionally. Differentially expressed genes (DEGs) were identified via microarray profiling of basal and IFN-γ/TNF-α-primed cells. miRNA-transcription factor (TF) coregulatory networks were constructed for key DEGs. In vivo, anti-hyperglycemic effects, islet regeneration, insulin expression, and local inflammation modulation were assessed in streptozotocin (STZ)-induced diabetic rats by transplanting dASCs, ndASCs, or IFN-γ-primed dASCs (p.dASCs).</p><p><strong>Results: </strong>DEGs in dASCs were significantly enriched in inflammation, glycerolipid metabolism, cell adhesion, cytoskeleton remodeling, angiogenesis, and insulin or hypoxia-related responses. EGFR/ERBB2 signaling, with downstream Ras/MAPK and PI3K/AKT cascades, and endocrine resistance-related pathways were significantly overrepresented. Although inflammatory responses were broadly shared, cytokine priming further exacerbated endocrine resistance and oxidative phosphorylation defects-associated transcriptomic signatures in dASCs. Key DEGs (EGFR, ERBB2, ESR1, FOS, IL1B, JUN, KRAS, MMP9, RUNX2) were identified as contributors to insulin resistance-related pathways and were used to construct a miRNA-TF coregulatory circuit for mechanistic and therapeutic hypothesis-generation. In the STZ-diabetes model, dASCs displayed limited regenerative capacity and attenuated immunomodulatory function; however, these potentials were partially restored by p.dASCs. Favorable trends in glycemic control parameters were observed with ndASCs, and C-peptide levels were significantly higher in p.dASC-treated rats compared with those receiving non-primed dASCs.</p><p><strong>Conclusion: </strong>The study suggests a multifaceted dysregulated transcriptomic signature in dASCs, prominently including endocrine resistance-related pathways. The therapeutic efficacy of dASCs is partially rescued by IFN-γ priming, which supports the potential of tailored preconditioning strategies for improving autologous cell therapy in diabetes.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"2879-2901"},"PeriodicalIF":4.9,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148158102","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":"Bioprinted Human Umbilical Cord Mesenchymal Stem Cell-laden Microfiber-derived Extracellular Vesicles Promote Endometrial Repair and Fertility Recovery in Intrauterine Adhesions.","authors":"Huan Yang, Jiayuan Xie, Jijie Zhan, Mengxiong Li, Yi Zhang, Boxun Liu, Jianwei Chen, Changlin Zhang, Tao Xu, Tian Li","doi":"10.1007/s12015-026-11165-x","DOIUrl":"10.1007/s12015-026-11165-x","url":null,"abstract":"<p><p>Intrauterine adhesions (IUAs) pose a significant reproductive health challenge, often leading to infertility and complications in pregnancy owing to endometrial damage and fibrosis. Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) therapy has emerged as a potential strategy for endometrial repair. However, traditional EVs production methods yield low quantities with limited efficacy, hindering their widespread application. In this study, we proposed an innovative approach that integrates three-dimensional (3D) bioprinted human umbilical cord MSC microfiber-derived EVs (3D-EVs) with gelatin methacrylate hydrogels for in situ delivery. Our platform achieved a 1,000-fold increase in 3D-EV particles production and superior cargo quality compared with conventional 2D cultures. In a rat endometrial organoid injury model, 3D-EVs and 2D-EVs exhibited equivalent therapeutic efficacy. 3D-EVs promoted cell activity and inhibited cell damage by transferring decorin, which inhibited LPS-induced p38 phosphorylation. In vivo, 3D-EVs improved pregnancy outcomes by reducing endometrial fibrosis and promoting endometrial proliferation. Our findings suggest that 3D-EVs derived from bioprinted human umbilical cord MSC-laden microfibers mitigate endometrial injury and fibrosis, improving pregnancy outcomes in IUAs. This study opens new avenues for the development of effective EV-based therapies for the treatment of IUAs.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"2902-2918"},"PeriodicalIF":4.9,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148151226","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":"CAR T-cell Therapy for Extramedullary Multiple Myeloma: from Early Response to Durable Disease Control.","authors":"Ziyi Yang, Mi Zhou, Yi Xiao","doi":"10.1007/s12015-026-11171-z","DOIUrl":"10.1007/s12015-026-11171-z","url":null,"abstract":"","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"2965-2967"},"PeriodicalIF":4.9,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13354695/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148199943","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":"Amniotic Fluid Stem Cells in Birth Defects: Integrated Roles in Disease Modeling, Prenatal Diagnosis, and Therapy.","authors":"Yuanhang Zhu, Xinyue Zhao, Zhongchen Hou, Jing Xue, Ping Zhang, Chenchen Ren, Ling Liu","doi":"10.1007/s12015-026-11161-1","DOIUrl":"10.1007/s12015-026-11161-1","url":null,"abstract":"<p><p>Birth defects impose a significant global health burden, driving an urgent need for improved prenatal diagnostic and therapeutic strategies. Amniotic fluid stem cells (AFSCs) have emerged as a uniquely advantageous cell source in this context. This review provides a comprehensive synthesis of the multifaceted roles of AFSCs in advancing fetal medicine. We begin by detailing their biological characteristics, including origin, heterogeneity, and markers, while highlighting how their properties are influenced by gestational and pathological factors. We then elaborate on their dual mechanisms of tissue repair, focusing on direct homing/engraftment and, predominantly, their potent paracrine and extracellular vesicle (EV)-mediated actions. The core of the review systematically examines the integrated applications of AFSCs across a clinical continuum: (1) in disease modeling, where they serve as a foundation for generating patient-specific induced pluripotent stem cells (iPSCs) and complex organoids to study genetic disorders; (2) in prenatal diagnosis, exploring their potential contribution to fetal microchimerism and cell-free fetal DNA to refine non-invasive testing; and (3) in therapeutic interventions, reviewing preclinical progress in treating conditions such as pulmonary hypoplasia, myelomeningocele, and hematopoietic diseases via transamniotic stem cell therapy (TRASCET) or EV administration. Finally, we discuss the current limitations, including standardization hurdles and mechanistic knowledge gaps and the promising future of AFSCs, underpinned by their ethical sourcing, ease of access, and strong regenerative potential. This work consolidates the evidence positioning AFSCs as a transformative, unified platform for innovating the prevention, diagnosis, and treatment of birth defects.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"2691-2703"},"PeriodicalIF":4.9,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148035333","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":"Immunometabolic Modulation of the Bone Marrow Niche by Bioactive Materials to Rescue Impaired Fracture Healing.","authors":"Dong Li, Shaolong Ma","doi":"10.1007/s12015-026-11162-0","DOIUrl":"10.1007/s12015-026-11162-0","url":null,"abstract":"<p><p>Despite advancements in mechanical fixation, impaired fracture healing remains a significant clinical challenge, largely driven by immunometabolic dysregulation within the bone marrow niche. Conditions such as prolonged M1 macrophage activation, disrupted metabolic homeostasis, and mitochondrial dysfunction collectively stall the regenerative cascade and push skeletal progenitors toward senescence or adipogenesis. This review comprehensively explores the paradigm shift from purely mechanical stabilization to immunometabolic reprogramming using bioactive materials to rescue impaired bone repair. We systematically categorize biomaterial-driven interventions into three core pillars: metal ion-releasing systems that orchestrate immune-osteogenic crosstalk, metabolism-targeted delivery platforms that suppress aerobic glycolysis to alleviate inflammatory stress, and mitochondria-protective strategies that scavenge reactive oxygen species to restore cellular bioenergetics. Furthermore, we emphasize the critical importance of spatiotemporal design-such as phase-matched degradation kinetics, sequential drug release, and localized deployment-to synchronize material function with physiological healing stages while minimizing ectopic ossification. Ultimately, integrating these advanced biomaterial strategies with emerging diagnostic tools, such as single-cell profiling, offers a promising framework for personalized, precision-guided therapies to overcome complex bone regeneration failures in compromised clinical scenarios.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"2704-2723"},"PeriodicalIF":4.9,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148043790","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":"From Single-cell Heterogeneity to Regenerative-medicine Accountability: A Global Readiness Passport for Stem-Cell Products.","authors":"M Vijayasimha, M Srikanth, Ravinder Kaur","doi":"10.1007/s12015-026-11178-6","DOIUrl":"10.1007/s12015-026-11178-6","url":null,"abstract":"","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"2972-2973"},"PeriodicalIF":4.9,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148228506","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":"The Influence of Fibroblast Microenvironment on the Differentiation and Maturation of Stem Cell-Derived Cardiomyocytes.","authors":"Yuliang Dong, Haozhe Jiang, Fan Zhou, Junsheng Mu","doi":"10.1007/s12015-026-11176-8","DOIUrl":"10.1007/s12015-026-11176-8","url":null,"abstract":"<p><p>Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) have emerged as a promising cell source for myocardial repair. However, iPSC-CMs generated in vitro exhibit an immature phenotype resembling the fetal stage in terms of morphology, electrophysiology, and metabolic properties, falling significantly short of the maturity observed in adult cardiomyocytes [1]. The differentiation and maturation of cardiomyocytes do not occur in isolation but are progressively realized within a specific cellular microenvironment. Cardiac fibroblasts (CFs) account for approximately 20%-30% of the total cell population in the heart. CFs play pivotal roles in cardiac development, homeostasis, and pathological remodeling through the secretion of various soluble factors, the synthesis and remodeling of the extracellular matrix (ECM), and the establishment of physical and functional intercellular connections (Fig. 1). CFs construct specific microenvironments that significantly influence the lineage commitment, early expansion, and subsequent structural and functional maturation of iPSC-CMs. Thus, the CF microenvironment acts as a crucial extrinsic factor regulating the fate of stem cell-derived cardiomyocytes.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"2974-2976"},"PeriodicalIF":4.9,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148266176","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}