STEM CELLS最新文献_第2页

"Quiescence" in the resting zone of the growth plate: a systematic review. 生长板静息带的“静止”：系统综述。

IF 3.6 2区医学

STEM CELLS Pub Date : 2026-04-25 DOI: 10.1093/stmcls/sxag010

Mahtab Avijgan, Amal Nazaraliyev, Klas Blomgren, David Gomez-Cabrero, Phillip T Newton

{"title":"\"Quiescence\" in the resting zone of the growth plate: a systematic review.","authors":"Mahtab Avijgan, Amal Nazaraliyev, Klas Blomgren, David Gomez-Cabrero, Phillip T Newton","doi":"10.1093/stmcls/sxag010","DOIUrl":"10.1093/stmcls/sxag010","url":null,"abstract":"Postnatal skeletal growth in childhood and adolescence depends on cartilage organs called (epiphyseal) growth plates. Studies in the last decade have identified populations of skeletal stem cells within mouse growth plates' resting zones. While cellular quiescence is vital for the maintenance of many tissue-resident stem cell populations, the resting zone chondrocytes have been labeled \"quiescent\" for decades. However, the features of cellular quiescence that have been reported in the postnatal resting zone, how they were defined or experimentally assessed, and knowledge gaps relative to other quiescent cell types, remain to be well described. To address this, we conducted a systematic review, using the PRISMA guidelines, to identify studies of resting zone chondrocytes including the prefix \"quiescen*.\" Definitions, keywords, chronological data and experimental findings were extracted. Our analysis demonstrated that, compared to those in other well-studied tissues, features of cellular quiescence in RZ chondrocytes remain poorly reported and underexplored, with limited molecular and functional characterization. Furthermore, while most identified studies reported changes in cell division parameters, integration between cues controlling resting zone cell quiescence is incomplete and heterogeneity among the various sub-populations of RZ cells/potential quiescent states is yet to be fully determined. This review identifies consensuses and knowledge gaps between studies and between quiescent RZ cells and those in other tissues and can act to enhance consistency and comparability in future studies of \"quiescence\" in the RZ chondrocytes.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13110114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147375562","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

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 3.6 2区医学

STEM CELLS Pub Date : 2026-04-24 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":"https://doi.org/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":3.6,"publicationDate":"2026-04-24","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

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 3.6 2区医学

STEM CELLS Pub Date : 2026-04-22 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":"https://doi.org/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":3.6,"publicationDate":"2026-04-22","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

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 3.6 2区医学

STEM CELLS Pub Date : 2026-04-17 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 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 cytoxicity 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":3.6,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Stem cells enhance mitochondrial function in experimental Huntington's disease. 干细胞增强实验性亨廷顿病的线粒体功能。

IF 3.6 2区医学

STEM CELLS Pub Date : 2026-04-09 DOI: 10.1093/stmcls/sxag019

Francesco D'Egidio, Napasiri Putthanbut, Michaela Starahs, Jea Young Lee, Cesario V Borlongan

{"title":"Stem cells enhance mitochondrial function in experimental Huntington's disease.","authors":"Francesco D'Egidio, Napasiri Putthanbut, Michaela Starahs, Jea Young Lee, Cesario V Borlongan","doi":"10.1093/stmcls/sxag019","DOIUrl":"https://doi.org/10.1093/stmcls/sxag019","url":null,"abstract":"Huntington's Disease (HD) is a neurodegenerative disorder caused by CAG triplet expansion in the HTT gene, producing a mutant Huntingtin protein that impairs mitochondrial dynamics by reducing fusion and increasing fission. Mesenchymal stem cells (MSCs) have shown potential therapeutic effects by sharing functional mitochondria and other secretomes. In this study, quinolinic acid-lesioned neuro-2a (QA-N2a) cells and glutamatergic neurons with 50 CAG repeats (HD neurons) were co-cultured with human umbilical cord-derived MSCs for 5 hours. For QA-N2a cells, immunocytochemistry was performed to demonstrate change in GABA and Substance P before and after co-culture. For HD neurons, immunocytochemistry was conducted to identify mitochondrial proteins, while Western Blot was employed to evaluate proteins related to inflammation and mitochondrial function. As a result, co-culture with MSC significantly restored the expression of GABA and Substance P, which diminished after QA exposure. In HD neurons co-cultured with MSCs, an increase in mitochondrial abundance was observed, with significantly higher intensity and dendritic distribution of mitochondria compared to control cells. Western Blot analysis confirmed this increase and showed a rising trend in ATP5a levels. MSCs also promoted mitochondrial fusion, indicated by higher levels of Mitofusin 2 (MFN2) and Mitochondrial Dynamin Like GTPase (OPA1), and a trend of reduction in the fission marker Dynamin-Related Protein (DRP1). Additionally, the co-culture led to a decreased trend in neuroinflammation markers IL-6, TNF-α, MMP9, and p-NFkB. Collectively, this study demonstrates that MSCs alleviate HD pathology by restoring mitochondria activity and potentially suppressing inflammation in two different HD in vitro models.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147669353","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

Cell Barcoding Reveals Lineage-dependent Outcomes in hiPSC Cardiac Differentiation. 细胞条形码揭示了hiPSC心脏分化的谱系依赖性结果。

IF 3.6 2区医学

STEM CELLS Pub Date : 2026-04-07 DOI: 10.1093/stmcls/sxag017

Sogu Sohn, Daylin Morgan, Cody Callahan, Katelyn Dockery, Amy Brock, Janet Zoldan

{"title":"Cell Barcoding Reveals Lineage-dependent Outcomes in hiPSC Cardiac Differentiation.","authors":"Sogu Sohn, Daylin Morgan, Cody Callahan, Katelyn Dockery, Amy Brock, Janet Zoldan","doi":"10.1093/stmcls/sxag017","DOIUrl":"10.1093/stmcls/sxag017","url":null,"abstract":"Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have potential applications in treating cardiovascular disease but are currently limited in their clinical translation. This can be attributed in large part to the complex molecular and cellular interactions that underly cardiac differentiation, with current differentiation approaches yielding heterogeneous outcomes due to inadequate understanding and control of these interactions. We hypothesize that clonal lineage-dependent responses to differentiation contribute to these heterogeneous outcomes, and as such cardiac differentiations can be improved by tracking and controlling for hiPSC clonal heterogeneity, a variable often overlooked in current differentiation approaches. \"Fate priming\", wherein clonal lineage identity determines differentiation fate, has been demonstrated in other stem cell differentiation pathways. We investigated fate priming in hiPSC cardiac differentiation using the ClonMapper cell barcoding platform to label, track, and isolate distinct hiPSC lineages from the same cell line. We show that certain hiPSC lineages preferentially differentiate into hiPSC-CMs or non-CMs. After isolating lineages with apparent fate priming, we found significant differences in cardiac differentiation outcomes between these single-clone populations and heterogeneous, multi-clone hiPSC populations. These findings indicate that lineage identity influences hiPSC cardiac differentiation outcomes.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147643461","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

Synergizing Stem Cells with Biomaterials for Therapeutic Angiogenesis in Ischemic Diseases. 干细胞与生物材料协同治疗缺血性疾病血管生成。

IF 3.6 2区医学

STEM CELLS Pub Date : 2026-04-07 DOI: 10.1093/stmcls/sxag018

Taiyan Ji, Jiajia Shi, Jing Yang

{"title":"Synergizing Stem Cells with Biomaterials for Therapeutic Angiogenesis in Ischemic Diseases.","authors":"Taiyan Ji, Jiajia Shi, Jing Yang","doi":"10.1093/stmcls/sxag018","DOIUrl":"https://doi.org/10.1093/stmcls/sxag018","url":null,"abstract":"Therapeutic angiogenesis (TA) is a promising strategy for treating ischemic diseases, mainly by targeting the angiogenesis pathways and cells, particularly VEGF and endothelial progenitor cells. Although stem cell therapy has been extensively investigated, its clinical translation remains limited by challenges such as poor cell retention, low survival rates, and inefficient integration. In this review, we propose a mechanism-based framework of angiogenesis to discuss how biomaterials act synergistically with stem cells mainly through two distinct pathways: enhancing paracrine capacity and promoting direct differentiation of vascular lineage cells for vascular repair. Firstly, we go through the scientific literature and clinical studies, and summary the researches on biomaterials serve as artificial microenvironments to improve the retention and secretory function of mesenchymal stem cells (MSCs) and adipose-derived stem cells (ADSCs), thereby maximizing the release of angiogenic factors such as VEGF, bFGF, NGF, microRNA and so on. Secondly, we explore how functionalized biomaterials guide the in situ recruitment of endothelial progenitor cells (EPCs) and support the structural maturation of induced pluripotent stem cell (iPSC)-derived endothelial cells. By integrating these mechanism-driven approaches, we offer new perspectives on future directions for preclinical research and clinical translation of biomaterial-based therapies. Overall, this review has examined the role of individual stem cells and biomaterials, especially enhanced angiogenesis by stem cells focusing on their mechanisms of action and preclinical and clinical applications. We further discussed the challenges encountered by stem cell therapy in advancing to the stage of clinical transformation and considered future prospects.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147643405","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

Dual Roles of MAPK-Mediated C/EBPβ Phosphorylation in Promoting Maturation and Suppressing EMT During Hepatocyte Differentiation from hESCs. mapk介导的C/EBPβ磷酸化在hESCs肝细胞分化过程中促进成熟和抑制EMT中的双重作用。

IF 3.6 2区医学

STEM CELLS Pub Date : 2026-04-03 DOI: 10.1093/stmcls/sxag016

Shoupei Liu, Xiangting Cao, Haibin Wu, Shuai Zhang, Xueyan Zhang, Sen Chen, Huanhuan Shan, Weili Gu, Yongjian Zhou, Yuyou Duan

{"title":"Dual Roles of MAPK-Mediated C/EBPβ Phosphorylation in Promoting Maturation and Suppressing EMT During Hepatocyte Differentiation from hESCs.","authors":"Shoupei Liu, Xiangting Cao, Haibin Wu, Shuai Zhang, Xueyan Zhang, Sen Chen, Huanhuan Shan, Weili Gu, Yongjian Zhou, Yuyou Duan","doi":"10.1093/stmcls/sxag016","DOIUrl":"https://doi.org/10.1093/stmcls/sxag016","url":null,"abstract":"Human embryonic stem cell (hESC)-derived hepatocytes (hEHs) display functional deficits, particularly impaired albumin secretion and ammonia metabolism, compared to primary human hepatocytes (PHHs). Here, we investigated the regulatory role of CCAAT/enhancer-binding protein beta (C/EBPβ) in hepatocyte maturation. Forced C/EBPβ expression enhanced hepatocyte functionality and upregulated hepatocyte-specific genes, while suppressing epithelial-mesenchymal transition (EMT) via downregulating canonical EMT markers. Mechanistically, CUT&Tag and luciferase reporter assays confirmed C/EBPβ directly binds to the promoter regions of CDH1 (E-cadherin) and CPS1 (carbamoyl phosphate synthetase 1). Co-immunoprecipitation identified an interaction between C/EBPβ and the MAPK pathway. RNA interference combined with Western blot analysis revealed that MAPK1-mediated phosphorylation of C/EBPβ at Thr-235 augmented its transactivation activity, accelerating hepatocyte maturation. Our findings establish C/EBPβ as a master regulator that coordinates transcriptional networks and post-translational modifications during hEHs maturation, providing novel insights for generating mature hepatocytes for disease modeling and regenerative medicine applications. The transcriptional activity of C/EBPβ is regulated by MAPK1 protein within the ERK/MAPK signaling pathway. MAPK1 moves from the cytoplasm into the nucleus and transfers phosphate groups to C/EBPβ. This process reverses the \"self-inhibition\" state of C/EBPβ and enhances its transcriptional activity on downstream target genes.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147626433","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

Stem Cell Therapies to Modulate Harmful Immune Responses in Kidney Disease: Progress Toward Clinical Validation. 干细胞疗法调节肾脏疾病的有害免疫反应：临床验证的进展

IF 3.6 2区医学

STEM CELLS Pub Date : 2026-03-28 DOI: 10.1093/stmcls/sxag015

Qifeng Ou, Fuxuan Li, Shengkun Wang, Ruixue Chen, Cuiqing Ma, Matthew D Griffin

{"title":"Stem Cell Therapies to Modulate Harmful Immune Responses in Kidney Disease: Progress Toward Clinical Validation.","authors":"Qifeng Ou, Fuxuan Li, Shengkun Wang, Ruixue Chen, Cuiqing Ma, Matthew D Griffin","doi":"10.1093/stmcls/sxag015","DOIUrl":"https://doi.org/10.1093/stmcls/sxag015","url":null,"abstract":"Stem cell therapies hold promise for halting or reversing kidney disease and improving kidney transplant (KTx) outcomes. One route to large-scale clinical application of stem cell therapies for kidney disease is through their capacity to modulate the balance between tissue injury and repair via crosstalk with other cells. Among the key disease-modulating effects of stem cells is their interaction with components of the immune system involved in harmful inflammation during acute kidney injury (AKI), chronic kidney disease (CKD) and complications of KTx. Extensive basic research demonstrates that stem cells employ diverse paracrine mechanisms to re-program immunological activities from pro-inflammatory/pro-fibrotic to anti-inflammatory/pro-repair. The therapeutic benefits of these effects are confirmed in many pre-clinical models of AKI, CKD and KTx for autologous and allogeneic stem cells including hematopoietic stem cells, mesenchymal stem cells, renal progenitor cells, and induced pluripotent stem cells. Nonetheless, translating these findings into therapeutic immunomodulatory cell products that improve the lives of those with kidney disease is highly challenging. The aims of this review are to: (a) Summarize recent insights into the common molecular and cellular mechanisms of immune-mediated tissue injury in kidney disease and KTx along with the types of stem therapies that have been developed to address them. (b) Critically evaluate the extent to which clinical trials of stem cell products have validated such effects in humans with kidney disease and KTx. (c) Identify key bottlenecks to the large-scale application of stem cell therapies to reduce the burden of kidney disease on patients and societies.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147571286","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

FAK inhibition following acute olfactory epithelial inflammation promotes neurogenesis and functional recovery through stem cell CNTF. 急性嗅觉上皮炎症后FAK抑制通过干细胞CNTF促进神经发生和功能恢复。

IF 3.6 2区医学

STEM CELLS Pub Date : 2026-03-26 DOI: 10.1093/stmcls/sxag011

Derek Cox, Brian Wang, Jaeden Pyburn, Morning Dove Rose, Diego J Rodriguez-Gil, Theo Hagg, Cuihong Jia

{"title":"FAK inhibition following acute olfactory epithelial inflammation promotes neurogenesis and functional recovery through stem cell CNTF.","authors":"Derek Cox, Brian Wang, Jaeden Pyburn, Morning Dove Rose, Diego J Rodriguez-Gil, Theo Hagg, Cuihong Jia","doi":"10.1093/stmcls/sxag011","DOIUrl":"10.1093/stmcls/sxag011","url":null,"abstract":"The sense of smell is maintained by regenerating olfactory sensory neurons (OSNs) from basal stem cells in the olfactory epithelium (OE). Acute inflammation destroys OSNs, causing hyposmia and anosmia, but activates basal cells. Manipulation of signaling pathways to promote basal cell proliferation and neuroregeneration would reveal novel therapeutic targets for smell deficits. We found that ciliary neurotrophic factor (CNTF) from horizontal basal cells (HBCs, quiescent stem cells) promotes neuroregeneration and functional recovery following methimazole-induced acute injury. Moreover, inhibition of focal adhesion kinase (FAK) upregulates CNTF in naïve OE. Here, we show that the small molecule FAK inhibitor increased CNTF expression in cultured primary HBCs isolated from methimazole-treated mice. Although methimazole-induced CNTF did not seem to be through FAK signaling, inducible cre-lox knockout of FAK in HBCs in mice further increased CNTF expression, as well as Mash1, a marker for globose basal cells (GBCs, neuronal progenitors), and GBC proliferation. Moreover, intranasal aspiration, but not systemic treatment, of a water-soluble pharmacological FAK inhibitor (FAK14) 3 days following methimazole, dose-dependently increased CNTF and Mash1 expression, and GBC proliferation. Intranasal FAK14 also enhanced methimazole-induced regeneration of new OSNs in CNTF+/+, but not in CNTF-/-, mice, demonstrating that FAK14 boosts neuroregeneration through additional CNTF following acute inflammation. Finally, intranasal FAK14 instillation following methimazole improved the functional recovery of smell. This study identifies the therapeutic potential of intranasal application of FAK inhibitors to enhance olfactory neuroregeneration and function following injury.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13064918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147375526","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