STEM CELLS最新文献_第4页

From bench to bedside: stem and progenitor cell-derived extracellular vesicles in cardiac therapy. 从实验室到床边：干细胞和祖细胞衍生的细胞外囊泡在心脏治疗中的应用。

IF 4.8 2区医学

STEM CELLS Pub Date : 2026-07-22 DOI: 10.1093/stmcls/sxag022

Carolina Balbi, Giulia A Vassalli-Sandal, Giuseppe Vassalli

{"title":"From bench to bedside: stem and progenitor cell-derived extracellular vesicles in cardiac therapy.","authors":"Carolina Balbi, Giulia A Vassalli-Sandal, Giuseppe Vassalli","doi":"10.1093/stmcls/sxag022","DOIUrl":"10.1093/stmcls/sxag022","url":null,"abstract":"Initially regarded as insignificant cellular waste, extracellular vesicles (EVs) are now recognized as key mediators of intercellular communication, capable of transferring bioactive molecules-such as proteins, nucleic acids, and small compounds-between cells. This function has positioned EVs as promising cell-free therapeutic agents with the potential to transform modern medicine. Stem and progenitor cells naturally release EVs that can replicate many of the therapeutic effects of cell transplantation, while avoiding the challenges associated with administering living cells. EVs derived from various cell sources-including embryonic stem cells, induced pluripotent stem cells, mesenchymal stem cells, stromal cells, cardiac progenitor cells, and endothelial progenitor cells-have shown therapeutic efficacy in preclinical models of ischemic heart disease. EVs' translation into human trials in cardiac therapy has lagged behind, however, largely due to challenges related to EV production standardization, regulatory frameworks, and the demonstration of reproducible efficacy in human subjects. Nevertheless, recent milestones have been achieved with the successful completion of the phase I EV-AMI trial (Safety Evaluation of Intracoronary Infusion of EVs in Patients with Acute Myocardial Infarction, NCT04327635) and the enrollment of the first patient in the phase I SECRET-HF trial (Treatment of Non-ischemic Cardiomyopathies by Intravenous Extracellular Vesicles of Cardiovascular Progenitor Cells, NCT05774509). This concise review outlines the evolution of EVs from basic biological discovery to innovative therapeutic platforms, with particular emphasis on their potential applications in acute myocardial infarction. Remaining challenges for clinical translation, including manufacturing and regulatory hurdles, will also be discussed.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147758461","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}

引用次数: 0

Application of human induced pluripotent stem cells for tissue modeling and therapy: are we on track? hipsc在组织建模和治疗中的应用：我们在轨道上吗？

IF 4.8 2区医学

STEM CELLS Pub Date : 2026-07-22 DOI: 10.1093/stmcls/sxag027

Mathew Nickel Maunu, Ingrid Meulenbelt, Yolande F M Ramos

{"title":"Application of human induced pluripotent stem cells for tissue modeling and therapy: are we on track?","authors":"Mathew Nickel Maunu, Ingrid Meulenbelt, Yolande F M Ramos","doi":"10.1093/stmcls/sxag027","DOIUrl":"10.1093/stmcls/sxag027","url":null,"abstract":"Stem cells are key for development of disease modeling and therapies. While promising, however, current application of cutting-edge hiPSC technologies is, among others, confounded by cellular heterogeneity leading to concerns about their suitability for experimental and clinical applications. Variations across donors, tissue sources, methodologies, and analytical challenges, together contribute to the observed heterogeneity. Hence, increased understanding of heterogeneity in stem cell research is essential to advance development of reliable tissue models and effective therapies. In this review, we summarize current knowledge regarding the origins of cellular heterogeneity in hiPSC-derivatives. Differentiation protocols can be improved through the application of novel media morphogens, integration with new biomaterials and physical strategies (eg, 3D culture, mechanical stimulation). Additionally, standardization of methods and regulations for generation and application of cell lines and neo-tissues, thorough characterization, central banking, and registration of cells will reduce variation and increase experimental reproducibility. As reliable reference datasets become more abundant the continuous development of analytical tools as well as advanced application of artificial intelligence to analyze omics datasets will become more refined. This will aid identification of different cell types in heterogeneous cell populations and key factors driving off-target differentiation. We provide recommendations for best practices throughout the stem cell research pipeline and discuss opportunities to advance broad applicability of stem cells for disease modeling and beyond through concerted efforts to improve experimental robustness and analytical accuracy. Finally, we advocate that certain heterogeneity may be essential in development of laboratory models to faithfully mimic the in vivo situation.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13401491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147831691","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}

引用次数: 0

Huntington's disease human lateral ganglionic eminence precursors differentiate into functionally mature medium spiny neurons exhibiting pathology. 亨廷顿氏病人类外侧神经节隆起前体细胞分化为功能成熟的中棘神经元，显示病理。

IF 4.8 2区医学

STEM CELLS Pub Date : 2026-07-22 DOI: 10.1093/stmcls/sxag025

Amy McCaughey-Chapman, Bronwen Connor

{"title":"Huntington's disease human lateral ganglionic eminence precursors differentiate into functionally mature medium spiny neurons exhibiting pathology.","authors":"Amy McCaughey-Chapman, Bronwen Connor","doi":"10.1093/stmcls/sxag025","DOIUrl":"10.1093/stmcls/sxag025","url":null,"abstract":"Huntington's disease (HD) is an autosomal dominant neurodegenerative disease characterized by the loss of GABAergic medium spiny neurons (MSNs). Cellular models of HD are mainly derived from human embryonic stem cells or induced pluripotent stem cells. These models are limited by their DNA embryonic age, low neuronal yields, and limited disease pathology. We propose direct reprogramming, which maintains the aging signature of the cells, to human induced lateral ganglionic eminence precursors (hiLGEP) results in the generation of high yields of functionally mature MSNs exhibiting pathological hallmarks of HD. hiLGEPs were derived from normal and HD fibroblasts by direct reprogramming and differentiated to MSNs. hiLGEP and MSN fate acquisition was compared between normal and HD through gene and protein expression. Known pathological hallmarks of HD were investigated within the hiLGEP-derived MSNs. The formation of functional synapses was investigated using live cell calcium imaging. We demonstrate that HD fibroblasts can be reprogrammed to hiLGEPs expressing key linage markers and displaying disease-related changes in expression of FOXP1 and FOXP2. HD hiLGEPs can be differentiated to high yields of MSNs co-expressing DARPP32, GABA, or GAD65/67, and SYN1 and PSD-95. HD MSNs show a reduced expression of BDNF, HAP1, TRKB, Rhes and PGC1α, exhibit MW8+ mHTT aggregates and display smaller cell somas, reduced total neurite length and reduced branched neurites when compared to normal MSNs. An administration of 100 µM dopamine was necessary to generate a calcium response in HD MSNs. This study establishes a directly reprogrammed hiLGEP-derived MSN model of HD which recapitulates pathological signatures.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13391162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147831739","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}

引用次数: 0

Transplantation of human stem cell-derived cone photoreceptors partially restores vision in aged rd1 mice with advanced retinal degeneration. 人类干细胞来源的视锥光感受器移植可部分恢复老年rd1小鼠的视力。

IF 4.8 2区医学

STEM CELLS Pub Date : 2026-06-27 DOI: 10.1093/stmcls/sxag023

Christopher A Procyk, Anna Melati, Menahil Tariq, Jingshu Liu, Matthew J Branch, Jamie D Delicata, Philippa Harding, Mahmoud Khazim, Majid Moshtagh Khorasani, Bryan Ladino, Emily P Lanning, Miriam Margari, Ifrax Mahamoud, Christi Mofidi, Krunal Narendra Kumar, Salome Van Heerden, Alexander J Smith, Emma L West, Robin R Ali, Rachael A Pearson

{"title":"Transplantation of human stem cell-derived cone photoreceptors partially restores vision in aged rd1 mice with advanced retinal degeneration.","authors":"Christopher A Procyk, Anna Melati, Menahil Tariq, Jingshu Liu, Matthew J Branch, Jamie D Delicata, Philippa Harding, Mahmoud Khazim, Majid Moshtagh Khorasani, Bryan Ladino, Emily P Lanning, Miriam Margari, Ifrax Mahamoud, Christi Mofidi, Krunal Narendra Kumar, Salome Van Heerden, Alexander J Smith, Emma L West, Robin R Ali, Rachael A Pearson","doi":"10.1093/stmcls/sxag023","DOIUrl":"10.1093/stmcls/sxag023","url":null,"abstract":"Targeted photoreceptor replacement therapy is a promising, potentially disease-agnostic approach for reversing sight-loss associated with advanced retinal degenerations, including age-related macular degeneration. We have previously shown that transplantation of human stem cell-derived cone photoreceptors (hCones) into young adult (3-month-old) mouse models of advanced retinal degeneration can restore retinal function. However, substantial remodeling of the remaining inner retinal circuitry continues long after complete photoreceptor loss, raising the critical question of whether photoreceptor transplantation can effectively rescue function at very late-stage degeneration. rd1 mice received transplants at 12-15 months of age and were examined ∼3 months later. Transplanted hCones survived in large numbers, while host inner retinal neurons exhibited significant plasticity, extending dendrites to transplanted hCones, and making synapse-like contacts. Host Müller glia undergo notable remodeling, apparently incorporating the donor cells within the retinal structure. Multielectrode array recordings showed robust rescue of light-evoked activity across the normal photopic range intensities and evidence of inner retinal processing, while some treated mice showed improvements in visually evoked optokinetic head tracking behavior. Together, these data indicate that effective rescue following photoreceptor replacement therapy is feasible long after complete photoreceptor loss and extensive inner retinal remodeling.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13312030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147831711","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}

引用次数: 0

Derivation of functional early gestation decidual natural killer cell subtypes from induced pluripotent stem cells. 诱导多能干细胞衍生功能性早孕蜕膜自然杀伤细胞亚型。

IF 4.8 2区医学

STEM CELLS Pub Date : 2026-06-27 DOI: 10.1093/stmcls/sxag020

Virginia Chu Cheung, Jennifer Jaimez, Carly DaCosta, Harneet Arora, Christine Caron, Jaroslav Slamecka, Manuel Fierro, Morgan Meads, Kathleen Fisch, Robert E Morey, Luisjesus S Cruz, Devika Pant, Dan S Kaufman, Mariko Horii, Jack D Bui, Mana M Parast

{"title":"Derivation of functional early gestation decidual natural killer cell subtypes from induced pluripotent stem cells.","authors":"Virginia Chu Cheung, Jennifer Jaimez, Carly DaCosta, Harneet Arora, Christine Caron, Jaroslav Slamecka, Manuel Fierro, Morgan Meads, Kathleen Fisch, Robert E Morey, Luisjesus S Cruz, Devika Pant, Dan S Kaufman, Mariko Horii, Jack D Bui, Mana M Parast","doi":"10.1093/stmcls/sxag020","DOIUrl":"10.1093/stmcls/sxag020","url":null,"abstract":"Abnormal decidual natural killer cell (dNK) function is linked to pregnancy complications occurring in both early and late gestation, including recurrent pregnancy loss, preeclampsia, and preterm birth. Exploration of dNK heterogeneity as it relates to function is an active area of research; however, most of this work has focused on early gestation. Using flow cytometric and transcriptomic single-cell definitions of dNK subtypes, we characterized dNK heterogeneity in term dNK within both chorioamniotic membranes and the basal plate. We also applied aptamer-based secretome profiling to first trimester and term dNK and found dNK-specific proteins-VEGF and PLGF-to be reduced at term. We further determined that, compared to first trimester dNK, term dNK have reduced cytotoxicity against target cells. Finally, we applied this knowledge to establish a protocol for differentiation of induced pluripotent stem cells (iPSC) into functional dNK. We found that treatment with TGFβ enriched for dNK2 subtype, while inducing dNK markers, CD9 and CD103. We evaluated function using cytokine and degranulation assays, aptamer-based secretome profiling, and cytotoxicity assays. We found that iPSC-dNK are functionally most similar to primary dNK. Further, TGFβ iPSC-dNK had reduced GM-CSF in response to PMA/I and increased secretion of VEGF and other first trimester-specific proteins-supportive of a shift towards an early gestation, dNK2-dominant, phenotype. We conclude that changes in dNK function across gestation reflect shifts in dNK subtypes that can be reproducibly derived from iPSC, providing a new method for modeling dNK and laying the foundation for cell-based therapeutics for reproductive disease.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13387357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721070","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}

引用次数: 0

Mesenchymal stem cell-based delivery systems for the treatment of brain tumors. 基于间充质干细胞的输送系统治疗脑肿瘤。

IF 4.8 2区医学

STEM CELLS Pub Date : 2026-06-27 DOI: 10.1093/stmcls/sxag024

Mohammad Amin Bakhshan, Leila Chodari, Sayyed Jafar Hasani, Mehran Molavand, Zahra Niknam

{"title":"Mesenchymal stem cell-based delivery systems for the treatment of brain tumors.","authors":"Mohammad Amin Bakhshan, Leila Chodari, Sayyed Jafar Hasani, Mehran Molavand, Zahra Niknam","doi":"10.1093/stmcls/sxag024","DOIUrl":"10.1093/stmcls/sxag024","url":null,"abstract":"Brain tumors rank among the most lethal cancer types, accounting for high mortality rates in both pediatric and adult populations. They present formidable therapeutic obstacles owing to their intrinsically aggressive biology, the complexity of their surrounding microenvironment, and the relatively poor efficacy of existing standard treatment modalities. Mesenchymal stem cells (MSCs) have garnered significant interest in oncology research due to their inherent ability to migrate selectively toward tumor sites and their versatility as delivery vehicles for a wide range of therapeutic agents. This review highlights the diverse therapeutic roles of MSCs and their derivatives, such as exosomes and engineered vectors, in brain tumor management. It encompasses key therapeutic strategies leveraging MSCs, including MSC-mediated delivery of chemotherapeutic agents, oncolytic viruses, and therapeutic genes; exosome-based interventions; nanotechnology-enhanced targeting precision; and the modulation of tumor behavior by engineered MSC-derived cytokines. Despite their promise, concerns remain regarding the potential for MSCs to promote tumor growth and the need for precise delivery systems. This review highlights the crucial need for additional research to refine MSC-based strategies, particularly through the rational engineering of MSCs and their derivatives for multimodal therapeutic applications, with the goal of enhancing specificity, efficacy, and safety in the treatment of malignant brain tumors.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147831663","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}

引用次数: 0

Exosomes secreted by ADMSCs preserve cartilage integrity in knee osteoarthritis via AMPK-mediated mitochondrial dynamics and apoptosis. ADMSCs分泌的外泌体通过ampk介导的线粒体动力学和细胞凋亡来保护膝关节骨性关节炎软骨的完整性。

IF 4.8 2区医学

STEM CELLS Pub Date : 2026-06-27 DOI: 10.1093/stmcls/sxag021

Jinliang He, Yang Liu, Lu Zhang, Nan Nan, Te Ba, Yanfang Gao, Junfeng Kang, Huiqin Hao

{"title":"Exosomes secreted by ADMSCs preserve cartilage integrity in knee osteoarthritis via AMPK-mediated mitochondrial dynamics and apoptosis.","authors":"Jinliang He, Yang Liu, Lu Zhang, Nan Nan, Te Ba, Yanfang Gao, Junfeng Kang, Huiqin Hao","doi":"10.1093/stmcls/sxag021","DOIUrl":"10.1093/stmcls/sxag021","url":null,"abstract":"Adipose-derived mesenchymal stem cell (ADMSC) exosomes have emerged as promising therapeutic agents for degenerative joint diseases, yet their molecular actions in knee osteoarthritis (KOA) remain inadequately defined. In this study, exosomes were isolated from ADMSCs under both physiological and IL-1β-induced inflammatory conditions and comprehensively characterized by NTA, TEM, and exosome marker expression. Both types of exosomes were efficiently internalized by chondrocytes, with uptake reaching saturation after 12 hours regardless of inflammatory status. Functional assays revealed that while exosomes from healthy ADMSCs (EXOs) significantly enhanced levels of mitochondrial fusion proteins and decreased fission marker in IL-1β-induced chondrocytes after 24 hours, these beneficial effects were absent in exosomes derived from inflamed ADMSCs (IL-1β EXOs). Notably, EXO treatment reduced intracellular ROS accumulation, boosted SOD2 levels, and diminished apoptotic cell rates in chondrocytes. In vivo, administration of EXOs to rats with ACLT-induced KOA markedly alleviated cartilage degeneration, restoration of mitochondrial dynamics, and suppression of inflammatory and matrix-degrading mediators. Transcriptomic analysis showed that EXOs activated gene expression programs related to fatty acid metabolism, oxidative phosphorylation, and AMPK signaling, while IL-1β EXOs enriched inflammatory and apoptotic pathways. Importantly, both genetic knockdown and pharmacological inhibition of AMPK abolished the restorative effects of EXOs on mitochondrial dynamics and on the reduction of apoptotic markers both ex vivo and in vivo. These findings demonstrate that exosomes secreted by ADMSCs preserve cartilage integrity in KOA via AMPK-mediated mitochondrial dynamics. This work supports AMPK-targeted modulation of mitochondrial dynamics by stem cell exosomes as a promising disease-modifying strategy for KOA.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147758524","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}

引用次数: 0

Correction to: Mitochondrial Transfer from Mesenchymal Stem Cells to Macrophages Restricts Inflammation and Alleviates Kidney Injury in Diabetic Nephropathy Mice via PGC-1α Activation. 更正：间充质干细胞向巨噬细胞的线粒体转移通过激活PGC-1α抑制糖尿病肾病小鼠的炎症并减轻肾损伤。

IF 4.8 2区医学

STEM CELLS Pub Date : 2026-06-27 DOI: 10.1093/stmcls/sxag031

引用次数: 0

Correction to: Critical role of the potential O-linked glycosylation sites of CXCR4 in cell migration and bone marrow homing of hematopoietic stem progenitor cells. 更正：CXCR4潜在的o链糖基化位点在造血干细胞祖细胞的细胞迁移和骨髓归巢中的关键作用。

IF 4.8 2区医学

STEM CELLS Pub Date : 2026-06-27 DOI: 10.1093/stmcls/sxag030

引用次数: 0

Brent A. Reynolds, pioneer of adult neural stem cell biology. Brent A. Reynolds，成体神经干细胞生物学的先驱。

IF 4.8 2区医学

STEM CELLS Pub Date : 2026-06-11 DOI: 10.1093/stmcls/sxag036