Stem Cell Reviews and Reports最新文献

{"title":"DMBT1 in Adipose-Derived Stem Cell-Derived Exosomes Participates in Alleviating Ferroptosis to Promote Diabetic Wound Healing.","authors":"Yan Liu, Jinnan Wang, Yujiao Cai, Xiaoke Zhu, Zhanyuan Yuan, Jiahui Dai, Dehui Che, Dongsheng Cao","doi":"10.1007/s12015-026-11201-w","DOIUrl":"10.1007/s12015-026-11201-w","url":null,"abstract":"<p><p>Diabetic wounds represent one of the most severe complications of diabetes, and their clinical management remains challenging. This study investigated the therapeutic potential of adipose-derived stem cell-derived exosomes (ADSCs-Exo) for diabetic wounds. We isolated ADSCs and their exosomes, and by using Transwell and CCK-8 assays, we found that ADSCs-Exo were associated with proliferation and migration of keratinocytes and fibroblasts, and that they also enhanced the angiogenic activity of endothelial cells in vitro. In contrast, these promotive effects were significantly attenuated when exosomes derived from ADSCs with DMBT1 knockdown via siRNA (ADSCs^siDMBT1-Exo) were applied. In a diabetic mouse model, ADSCs-Exo treatment significantly accelerated wound healing, whereas the pro-healing capacity of ADSCs^siDMBT1-Exo was markedly reduced. To further explore the underlying mechanism, we performed RNA sequencing, which suggested that ADSCs-Exo might exert their therapeutic effects by alleviating ferroptosis and promoting cell proliferation. Subsequent experiments, including TEM, ROS assays, JC-1 staining, and tissue immunofluorescence, provided further support for these mechanistic findings. In summary, this study demonstrates that DMBT1 in ADSCs-Exo participates in alleviating ferroptosis in diabetic wound tissue, which may contribute to creating a favorable microenvironment for cell proliferation and promoting wound healing. This discovery provides a novel potential therapeutic target and strategy for the clinical treatment of diabetic wounds.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"3329-3346"},"PeriodicalIF":4.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148621082","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":"Artificial Blood and Stem Cell-Derived Oxygen Therapeutics in Oncology: Emerging Strategies for Overcoming Tumor Hypoxia.","authors":"Kamini Shivhare, Syed Shadab Raza","doi":"10.1007/s12015-026-11187-5","DOIUrl":"10.1007/s12015-026-11187-5","url":null,"abstract":"<p><p>Tumor hypoxia represents one of the primary obstacle in effective cancer therapy by conferring drug resistance to chemotherapy, radiotherapy, and immunotherapy, and facilitating tumor growth and immune escape. The use of artificial oxygen carriers (AOCs) represents an innovative approach to overcoming hypoxia and improving therapeutic efficacy in oncology. Here, we review some of the most recent studies on various oxygen-carrying systems, such as hemoglobin-based oxygen carriers (HBOCs), perfluorocarbon-based therapeutic agents, oxygen-releasing biomaterials, and induced pluripotent stem cell-derived RBCs (iPSC-RBCs). Recent advancements, including hemoglobin modifications, encapsulation techniques, and bio-inspired oxygen carriers, have improved the stability, biocompatibility, and circulation time of these platforms. Preclinical evidence indicates that these therapies increase oxygen concentration in tumors and sensitize them to radiation therapy, chemotherapy, and immunotherapy. Nonetheless, several issues associated with the use of these therapies such as oxidative toxicity, nitric oxide scavenging, poor blood circulation time, production complications, and risks observed in earlier studies, still need to be addressed. In addition, while iPSC-derived RBCs could offer hope for future transfusion use, but their use against tumors has not been fully explored yet. In summary, artificial oxygen therapies represent an innovative treatment strategy for overcoming treatment resistance that results from hypoxia in cancer. However, further studies are required to optimize these technologies and evaluate their clinical potential. The next generation of oxygen therapies must prioritize safety, tumor specificity, and the integration of oxygen delivery with anticancer therapies.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"3104-3116"},"PeriodicalIF":4.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148449499","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":"Homing and Migration of Umbilical Cord Mesenchymal Stromal Cells in Clinical Applications: Molecular Mechanisms, Translational Barriers, and Therapeutic Optimization.","authors":"XueXia Liu, FuJun Liu","doi":"10.1007/s12015-026-11210-9","DOIUrl":"10.1007/s12015-026-11210-9","url":null,"abstract":"<p><p>Umbilical cord-derived mesenchymal stromal cells (UC-MSCs) offer distinct advantages for clinical translation, including accessibility, scalability, and broad immunomodulatory capacity. However, the efficacy of systemically delivered UC-MSCs is constrained by suboptimal in vivo trafficking. Intravascular administration is limited by pulmonary first-pass sequestration, inefficient endothelial recruitment, blood-mediated inflammatory injury, and poor retention. While UC-MSCs homing is often conceptualized through a leukocyte adhesion paradigm, this model incompletely describes culture-expanded UC-MSCs, which exhibit heterogeneous expression of chemokine receptors, adhesion molecules, and selectin ligands. Furthermore, biodistribution and safety are critically determined by biophysical and hemocompatibility parameters, including cell size, deformability, cryopreservation status, and tissue factor (TF/CD142)-dependent procoagulant activity. This review synthesizes current understanding of UC-MSCs trafficking at the translational interface of biology and manufacturing. We examine canonical migratory mechanisms-chemokine signaling, integrin-mediated adhesion, extracellular matrix remodeling, and intracellular motility pathways-alongside underappreciated determinants of therapeutic performance: instant blood-mediated inflammatory reaction (IBMIR), complement-coagulation crosstalk, post-thaw functional impairment, donor variability, and route-dependent biodistribution. We also address the paradox wherein therapeutic benefit occurs despite minimal durable engraftment, implicating paracrine signaling, extracellular vesicles, and apoptosis-associated immune reprogramming as primary effectors. Finally, we evaluate strategies to enhance delivery and efficacy, including preconditioning, glycoengineering, receptor overexpression, route optimization, biomaterial-assisted retention, and migration-relevant potency assays under Good Manufacturing Practice (GMP). Advancing UC-MSCs therapy toward reproducible, mechanism-guided clinical application requires rigorous integration of hemocompatibility assessment, product characterization, and clinically informative cell tracking.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"3248-3261"},"PeriodicalIF":4.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148685796","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":"Cell Therapy as Metabolic Rescue after Ischemic Stroke: Rewiring Bioenergetics, Redox Homeostasis, and Neurovascular Repair.","authors":"Salar Bakhtiyari, Iraj Alipourfard","doi":"10.1007/s12015-026-11200-x","DOIUrl":"10.1007/s12015-026-11200-x","url":null,"abstract":"<p><p>Ischemic stroke represents a dynamic metabolic disorder of the neurovascular unit (NVU) rather than a static vascular occlusion followed by neuronal demise. Immediate oxygen and glucose deprivation rapidly deplete ATP, disrupt the transmembrane ionic gradients, increase glutamate excitotoxicity, and overload mitochondrial with calcium. These events alter glycolytic, lipid, amino acid, and redox pathways. During the subacute and chronic phases, astrocytes, microglia, macrophages, endothelial cells, pericytes, oligodendrocytes, and surviving neurons continue to remodel substrate utilization. These phase-specific metabolic programs either accelerate infarct expansion and blood-brain barrier disruption or facilitate angiogenesis, synaptic plasticity, and tissue repair. Consequently, cell-based therapeutic paradigms have shifted from direct neuronal replacement toward metabolic rescue. Transplanted cells and cell-free derivatives deliver trophic factors, extracellular vesicles, microRNAs, antioxidant signals, mitochondrial cues, and immunoregulatory factors. These signals enhance mitochondrial fitness, restore redox homeostasis, attenuate pro-inflammatory glycolysis, and stabilize endothelial-pericyte coupling to stabilize a permissive neurorehabilitation microenvironment. This review synthesizes post-stroke metabolic landscapes and evaluates how mesenchymal stromal, neural stem/progenitor, endothelial progenitor, cord blood-derived, and mononuclear cells, and extracellular vesicles, may be incorporated into a phase-specific translational framework supported by target-engagement biomarkers and standardized potency assays.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"3196-3208"},"PeriodicalIF":4.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148607586","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":"Research Progress on Biomaterial Scaffolds Carrying Stem Cells for Inflammation Regulation After Spinal Cord Injury.","authors":"Nanjian Xu, Xiaoyin Chai, Weihu Ma, Weihu Zhang, Fang Yang","doi":"10.1007/s12015-026-11182-w","DOIUrl":"10.1007/s12015-026-11182-w","url":null,"abstract":"<p><p>The inflammatory cascade triggered by spinal cord injury (SCI) presents a major barrier to tissue repair. This review summarizes recent advances in this field. It outlines the selection criteria for different scaffold materials and stem cells. It also describes key strategies for the coordinated regulation of the inflammatory microenvironment, including structural support and immunomodulation. In addition, the review discusses cell-free therapies and the functionalization of stem cell-derived materials. Intelligent responsive systems are also highlighted. Furthermore, this article evaluates the validation of these approaches in preclinical models. It also examines the challenges associated with their clinical translation. Finally, emerging trends, including dynamic adaptation, functional integration, and precise regeneration, are discussed. This review aims to provide a theoretical foundation and to guide future research on combination therapies for SCI.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"2999-3019"},"PeriodicalIF":4.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148309464","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":"Targeted Strategies of Adipose Stem Cells for Metabolic Diseases: Mechanisms and Clinical Translation Challenges.","authors":"Menghan Chen, Siqi Ding, Wanying Chen, Yanming Chen, Liqun Li, Yucang He, Hao Dai","doi":"10.1007/s12015-026-11186-6","DOIUrl":"10.1007/s12015-026-11186-6","url":null,"abstract":"<p><p>Metabolic diseases, such as obesity, type 2 diabetes mellitus, non-alcoholic fatty liver disease, and atherosclerosis, represent a growing global health burden. Adipose-derived stem cells (ADSCs) have emerged as promising therapeutic agents due to their multipotency, paracrine activity, and potential for engineering targeted interventions. This review highlights recent advances in targeted ADSC strategies, focusing on their mechanisms, clinical applications, and translational challenges. Key targeted approaches include engineered exosomes for precise immunomodulation, surface-modified ADSCs for enhanced tissue homing, and biomaterial-based delivery systems for sustained and local release. Preclinical studies have demonstrated that these strategies can significantly improve glucose homeostasis, reduce hepatic steatosis, and alleviate chronic inflammation. However, clinical translation faces hurdles, including donor-dependent heterogeneity, a lack of standardized protocols, and insufficient long-term safety data. Future efforts should prioritize the development of precision-targeted ADSC therapies through genetic engineering, functionalized biomaterials, and rigorously controlled clinical trials to fully exploit their potential to treat metabolic diseases.BackgroundMetabolic diseases are prevalent worldwide, with conditions such as metabolic dysfunction-associated steatotic liver disease(MASLD), obesity, type 2 diabetes mellitus, and atherosclerosis affecting hundreds of millions of individuals. Existing therapies struggle to address the root causes of these conditions, creating an urgent clinical need. ADSCs have gained attention as a research hotspot due to their multifunctionality; however, the literature indicates that their clinical translation faces obstacles, including cellular heterogeneity, the absence of standardized protocols, and unresolved safety concerns. This review aims to review and summarize the research progress on targeted ADSC strategies for metabolic diseases, clarify their mechanisms of action, review preclinical and clinical evidence, and provide directions to overcome translational bottlenecks.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"3020-3032"},"PeriodicalIF":4.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148353504","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":"Photobiomodulation Therapy and Wnt/β-Catenin Signaling in Periodontal Ligament Stem Cells: is there a Mechanistic Link Accelerating Orthodontic Tooth Movement?","authors":"Rashin Bahrami, Maryam Pourhajibagher, Abbas Bahador","doi":"10.1007/s12015-026-11208-3","DOIUrl":"10.1007/s12015-026-11208-3","url":null,"abstract":"","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"3403-3405"},"PeriodicalIF":4.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148679748","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 Gene Function to Precision Intervention: CRISPR/Cas9 and Stem Cell-Based Strategies as Emerging Disease-Modifying Approaches in PMOS.","authors":"Masuma Khatun, Karolina Lundin, Timo Tuuri, Terhi Piltonen, Juha S Tapanainen, Andres Salumets","doi":"10.1007/s12015-026-11188-4","DOIUrl":"10.1007/s12015-026-11188-4","url":null,"abstract":"<p><p>Polyendocrine metabolic ovarian syndrome (PMOS) is a complex endocrine-metabolic disorder affecting up to 18% of women worldwide and remains the leading cause of anovulatory infertility. Despite extensive research, current treatments primarily target symptoms, including menstrual irregularities, hyperandrogenism, and metabolic dysfunction, without addressing the underlying molecular and tissue-level disturbances. Advances in multi‑omic profiling have identified disruptions across neuroendocrine, metabolic, inflammatory, and extracellular matrix pathways, alongside genetic susceptibility at loci such as DENND1A, CYP17A1, LHCGR, FSHR, IRS1, and PPARG. However, the functional roles of many variants remain unresolved. CRISPR/Cas9 gene editing enables precise interrogation of these pathways, while stem cell-based platforms, including mesenchymal stem cells (MSCs), exosomes, and gene-edited induced pluripotent stem cells (iPSCs), may serve as complementary platforms for regeneration and disease modeling. Preclinical studies demonstrate that MSCs and their derivatives modulate inflammation, restore ovarian structure, and improve metabolic parameters, while iPSC-based models enable patient-specific investigation of steroidogenic and metabolic abnormalities. Translational challenges remain, including targeted delivery, off-target effects, phenotypic heterogeneity, and regulatory considerations. Integrating CRISPR‑based functional genomics with stem cell research may shift PMOS management from symptom‑focused care to targeted, mechanism‑driven interventions that could modify the course of PMOS (Graphical Abstract).</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"3056-3080"},"PeriodicalIF":4.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148397656","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 Cell-Derived Exosomes: A Cell-Free Frontier in Peripheral Nerve Regeneration.","authors":"Lin Lin, Lin Yan, Yaqiong Zhu, Yukun Luo","doi":"10.1007/s12015-026-11192-8","DOIUrl":"10.1007/s12015-026-11192-8","url":null,"abstract":"","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"3384-3387"},"PeriodicalIF":4.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148472859","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 Communication Networks in the Bone Microenvironment: From the Maintenance of Homeostasis to Translational Interventions for Bone Diseases.","authors":"Wentao Wang, Kun Wang, Wenjing Wang, Xuan Mu, Zhiquan Cheng, Guangzhi Zhang, Xuewen Kang, Yonggang Wang","doi":"10.1007/s12015-026-11190-w","DOIUrl":"10.1007/s12015-026-11190-w","url":null,"abstract":"<p><p>Intercellular mitochondrial transfer has recently emerged as an important concept in bone biology, providing a new framework for understanding immune-metabolic cross-talk within the bone microenvironment. This microenvironment is a dynamic system that is both metabolically active and immunologically complex, and its homeostasis relies on finely tuned communication among multiple cellular populations. Increasing evidence suggests that mitochondrial transfer is a key mechanism integrating these diverse signaling networks. In this review, we systematically summarize recent advances in mitochondrial transfer among osteolineage cells, immune cells, and vascular-associated cells, and we further discuss its multiple roles in bone remodeling, tissue repair, and the pathogenesis of osseous diseases. At the mechanistic level, special emphasis is placed on the Mitochondrial Rho GTPase 1 (MIRO1)-mediated mitochondrial transport pathway, through which mitochondria are transferred from osteolineage cells to myeloid cells, thereby driving metabolic reprogramming and modulating susceptibility to ferroptosis, ultimately helping to suppress excessive osteoclastogenesis. From a pathological perspective, dysregulated mitochondrial transfer is increasingly recognized as a common feature across a range of skeletal disorders. In glucocorticoid-induced osteoporosis (GIOP), impairment of MIRO1-dependent mitochondrial transport promotes ferroptosis resistance in osteoclast precursors. In osteoarthritis, aberrant mitochondria accelerate cartilage degeneration by disrupting coenzyme A (CoA) metabolism through Nudix Hydrolase 8 (NUDT8) and subsequently activating the cGAS-STING signaling pathway. In bone metastasis, inflammatory signals triggered by mitochondrial deoxyribonucleic acid (mtDNA) release exhibit both pro-tumorigenic and anti-tumorigenic regulatory effects. Based on these mechanisms, this manuscript also critically evaluates the translational potential of several therapeutic strategies, including mesenchymal stem cell-derived mitochondrial transplantation, nanocarrier delivery systems, and the modulation of tunneling nanotubes. Overall, targeting intercellular mitochondrial transport may offer new therapeutic opportunities for metabolic intervention and immunomodulation in bone diseases.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"3131-3151"},"PeriodicalIF":4.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148498013","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}