STEM CELLS最新文献

{"title":"iPSC-derived modeling of HLA-lacking hematopoiesis reveals clonal diversity in eltrombopag response in acquired aplastic anemia.","authors":"Honoka Takahashi, Luna Seoka, Rio Takahashi, Yoshinori Yoshida, Kazuhisa Chonabayashi, Katsuto Takenaka, Koichi Akashi, Hiroyuki Takamatsu, Tatsuya Imi, Yoshitaka Zaimoku, Kohei Hosokawa, Takamasa Katagiri","doi":"10.1093/stmcls/sxag004","DOIUrl":"10.1093/stmcls/sxag004","url":null,"abstract":"<p><p>Acquired aplastic anemia (AA) is an immune-mediated bone marrow failure in which cytotoxic T lymphocytes (CTLs) target hematopoietic stem cells (HSCs). Approximately 30% of AA patients develop immune escape clones lacking specific HLA class I alleles (HLA[-]) through loss of heterozygosity in chromosome 6p (6pLOH) or somatic loss-of-function mutations. Eltrombopag (EPAG), a thrombopoietin receptor agonist (TPO-RA), demonstrates clinical efficacy in AA in combination with immunosuppressive therapy; however, its impact on HLA(-) HSCs and hematopoietic progenitor cells (HPCs) remains poorly understood. In this study, we evaluated the hematopoietic effects of EPAG using umbilical cord blood-derived HPCs and a humanized hematopoiesis model in immunodeficient (BRGS) mice. Furthermore, we established induced pluripotent stem cell (iPSC)-derived hematopoietic models encompassing five wild-type (WT) clones and seven HLA-lacking clones, differentiated them into HPCs, and assessed their responses to EPAG. EPAG selectively conferred a proliferative advantage to specific hematopoietic fractions in HLA(-) HPCs, distinct from that observed in WT HPCs. Molecular analyses revealed clone-dependent differences in CD110 expression and downstream effectors, including phosphorylated STAT5, FOXM1, and E2F1, indicating differential activation of TPO receptor-mediated signaling pathways among clones. These findings highlight the functional diversity of HLA(-) hematopoiesis and suggest that the hematopoietic response to EPAG is governed by clone-intrinsic signaling programs. Furthermore, our results provide new insights into how eltrombopag modulates clonal competition and hematopoietic recovery in immune-escape hematopoiesis, with potential implications for optimizing therapeutic strategies and predicting clinical response in patients with acquired AA.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146045866","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}

{"title":"Circadian timing optimizes allo-HSCT to prevent aGVHD: a breakthrough in chrono-immunotherapy.","authors":"Xiaguang Huang, Hening Xu, Yanru Xia, Zeshan Lu, Shiwei Duan, Yongming Xia","doi":"10.1093/stmcls/sxaf084","DOIUrl":"10.1093/stmcls/sxaf084","url":null,"abstract":"<p><p>Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is widely regarded as the most potent curative cell therapy for a range of malignancies, particularly hematologic cancers. However, its clinical application remains significantly constrained by acute graft-versus-host disease (aGVHD), a severe and potentially fatal complication. As such, developing more effective strategies to prevent and manage aGVHD has become an urgent priority in the field. In a groundbreaking study, the team led by Zhan Cheng and Zhu Xiaoyu introduced a novel time-based approach, revealing that the biological rhythm regulating the immune microenvironment can be harnessed to optimize the timing of hematopoietic stem cell infusion. Their findings demonstrate that this chronotherapeutic strategy can significantly reduce the incidence of aGVHD, offering a simple, drug-free, and cost-free innovation to improve outcomes in allo-HSCT.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145916200","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}

{"title":"A mouse growth plate injury model identified contributions of pdgfra and pdgfrb cellular descendants to bony bar formation.","authors":"Zhao Li, Myles Zhou, Xin Xing, Beicheng Du, Mary Archer, Chunbao Rao, Manyu Zhu, Aaron W James","doi":"10.1093/stmcls/sxag014","DOIUrl":"https://doi.org/10.1093/stmcls/sxag014","url":null,"abstract":"<p><p>Growth plate injuries in pediatric patients can lead to serious musculoskeletal complications, such as bony bar formation and potential growth arrest. Current clinical treatments have significant limitations, necessitating improved research models. The present study developed a highly reproducible drill-hole injury model in the mouse distal femur and introduces a quantitative scoring system for assessing bony bar formation. Using micro-computed tomography (μCT) and histological analyses, we demonstrate a progressive increase in bone tissue formation over a 42-day period. A 5-point grading system was developed to evaluate bony bar extent, validated through radiological and histological comparisons. We further examine the utility of the model by injuring either transgenic mice with lineage tracing for platelet-derived growth factor receptor alpha (Pdgfra) or beta (Pdgfrb). While not present before injury, both Pdgfra and Pdgfrb reporter+ cells migrate into sites of growth plate injury and participate in bony bar formation. In sum, this model offers a standardized, reproducible, and validated approach to quantitatively study growth plate injury mechanisms, facilitating the use of transgenic animal models or the development of new therapeutic strategies in pediatric orthopaedics.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147508206","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}

{"title":"LARP7 Enhances the Potential of Dental Pulp Stem Cells to Promote Peripheral Nerve Repair.","authors":"Zihan Yang, Guanlin Qu, Xiping Wang, Li Wang, Lu Chen, Guiqiang Fu, Wenze Chen, Zitong Yang, Wenjing Li, Yuqiong Zhou, Jiacheng Jin, Linxi Zhou, Duohong Zou","doi":"10.1093/stmcls/sxag013","DOIUrl":"https://doi.org/10.1093/stmcls/sxag013","url":null,"abstract":"<p><strong>Background: </strong>Peripheral nerve injuries (PNIs) present a persistent clinical challenge because of the intrinsically limited regenerative capacity of peripheral nerves. While dental pulp stem cells (DPSCs) exhibit significant neuroregenerative potential, their therapeutic efficacy is constrained by hostile microenvironments and inherent functional heterogeneity. Genetic modification may offer a promising strategy to enhance their therapeutic capabilities.</p><p><strong>Methods: </strong>DPSCs were induced toward neural lineage differentiation, and key gene candidates were identified through qRT-PCR. Lentiviral-mediated gene interference was performed to modulate target gene expression, followed by comprehensive analysis of differentiation outcomes using qRT-PCR, Western blotting, and immunofluorescence assays. RNA sequencing was employed to uncover associated signaling pathways, which were subsequently validated through pharmacological inhibition with specific inhibitors. The therapeutic efficacy of genetically engineered DPSCs was evaluated in a rat model of sciatic nerve crush injury, with neural regeneration quantitatively assessed via neuroelectrophysiological measurements and histological analyses.</p><p><strong>Results: </strong>LARP7 positively regulated the Schwann cell-like differentiation of DPSCs, as well as their trophic and anti-inflammatory effects, thus enhancing its therapeutic effects on nerve repair and promoting functional recovery. Mechanistically, we found that LARP7 remodeled cytokine-cytokine receptor interactions, enhancing trophic support while attenuating proinflammatory responses, and activated the PI3K-Akt-mTOR signaling pathway, with ERBB4 serving as a critical downstream effector, promoting DPSC differentiation into Schwann cell-like phenotypes.</p><p><strong>Conclusions: </strong>Collectively, LARP7-mediated changes in DPSCs establish a new therapeutic paradigm that addresses the limitations of current stem cell-based interventions and enables the development of standardized biotherapeutics for peripheral nerve repair.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147430017","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}

{"title":"Disease modeling of myocilin mutation-dependent normal tension glaucoma: human retinal ganglion cell susceptibility to unfolded protein response and mTOR signaling.","authors":"Subrata Kumar Shil, Murali Subramani, Matthew J Van Hook, Fang Qiu, Iqbal Ahmad","doi":"10.1093/stmcls/sxag009","DOIUrl":"10.1093/stmcls/sxag009","url":null,"abstract":"<p><p>Glaucoma represents a group of diseases where the unifying theme is the progressive degeneration of retinal ganglion cells (RGCs), causing irreversible vision loss. Mutations in the myocilin (MYOC) gene represent one of the most common genetic factors associated with primary open-angle glaucoma (POAG). However, the mechanism underlying MYOC mutation-associated POAG is poorly understood. Here, using human disease modeling of MYOC mutation (A445V)-dependent POAG, which is usually without ocular hypertension, we have tested a hypothesis that human RGCs (hRGCs) are the target of the mutant protein, making them vulnerable to degenerative changes. Examination of hRGCs generated from MYOCA445V POAG patient-specific induced pluripotent stem cells (iPSCs) revealed that their differentiation is adversely affected, compared to those generated from isogenic control iPSCs. Retinal ganglion cells regulatory and axon growth and guidance gene expression is decreased in patient-specific hRGCs vs isogenic controls. Consequently, the former display immature neurites and their ability to form synapses with the target cells and regenerate are compromised. Furthermore, they display immature networking physiology compared to isogenic controls. The pathological burden of the mutant protein is reflected in their preferential retention in the endoplasmic reticulum (ER) of patient-specific hRGCs, activating the unfolded protein response (UPR) toward mutation-associated developmental phenotype. Furthermore, we demonstrate that REDD1, a stress-induced factor, is a mechanistic link between the MYOCA445V-activated UPR axis and inhibited mTOR signaling, a critical regulator of RGC development and function. Ours is the first demonstration of MYOC mutation-dependent hRGC phenotype and posits a mechanism for hRGC susceptibility toward degeneration independent of ocular hypertension.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13017134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146224698","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}

{"title":"Stem cell and bioengineering approaches for end-stage renal disease: a comprehensive review.","authors":"Yusuke Nishimura","doi":"10.1093/stmcls/sxag003","DOIUrl":"10.1093/stmcls/sxag003","url":null,"abstract":"<p><p>End-stage renal disease (ESRD) is a major global health burden, and current treatments, such as dialysis and kidney transplantation, remain constrained by donor shortages, procedure-related complications, and reduced long-term quality of life. Regenerative medicine, particularly stem cell-based approaches, offers promising next-generation strategies for kidney repair and replacement. This review summarizes the current understanding of kidney development and intrinsic regenerative capacity and evaluates the therapeutic potential of hematopoietic stem cells, mesenchymal stem cells (MSCs), kidney-derived stem cells, and induced pluripotent stem cell (iPSC)-derived kidney organoids. Evidence from preclinical models demonstrates renoprotective and immunomodulatory effects across multiple stem cell types, whereas early-phase clinical trials have reported favorable safety profiles and preliminary signals of the efficacy of MSC-based therapies. iPSC- and organoid-based approaches present additional challenges, including incomplete vascularization, immature nephron structures, risks of tumorigenicity, immune compatibility issues, and the need for reproducible good manufacturing practice (GMP)-compliant manufacturing. Advances in biomaterials, organoid engineering, and vascularization strategies may help overcome these barriers. Overall, stem cell-based regenerative therapies show substantial potential to complement or ultimately reduce the reliance on dialysis and transplantation. Continued technological innovations and rigorously designed clinical trials are critical to translate these promising approaches into clinical practice.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146008034","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}

{"title":"Profiling the secretome: maternal obesity impacts redox and adipogenic signaling during neonatal mesenchymal stem cell adipogenesis.","authors":"Sofía Bellalta, Erika Pinheiro-Machado, Paola Casanello, Marijke Faas, Torsten Plösch","doi":"10.1093/stmcls/sxag001","DOIUrl":"10.1093/stmcls/sxag001","url":null,"abstract":"<p><p>Recent studies evidence an altered bioenergetic profile and higher adipogenic commitment in the mesenchymal stem cells (MSC) from neonates of mothers with obesity. We hypothesize that these alterations may also affect the secretome of these cells. The aim of this study was to characterize the secretome of MSCs from the offspring of women with obesity compared to the ones from normal-weight women, both before and during adipogenesis. Wharton's jelly-derived MSCs were isolated from newborns of normal-weight women (NW-MSC; Body Mass Index 18.5-24.5 kg/m2) and women with obesity (OB-MSC; Body Mass Index > 30 kg/m2) and cultured for 0, 5, and 21 days of adipogenesis. The secretome from these cells was collected during the three timepoints and characterized by mass spectrometry. Our findings reveal fundamental differences in the secretome profiles, primarily associated with pathways involved in cellular and metabolic processes. Maternal obesity was found to decrease redox capacity at day 0 but subsequently triggered a compensatory increase in redox proteins during adipogenesis of OB-MSCs. Additionally, OB-MSCs secreted higher levels of lipid synthesis-related proteins and proinflammatory adipokines, which may contribute to the dysregulated adipogenesis observed in obesity. These preliminary data indicate that maternal obesity programs the secretome of neonatal MSCs, supporting the hypothesis that maternal obesity imprints early progenitor cells and potentially dictates the future metabolic status of the offspring's adipocytes.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13026406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948196","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}

{"title":"Nicotinamide salvage is required for proliferation and sustaining self-renewal in undifferentiated embryonic stem cells.","authors":"Mu-Jie Lu, Hsin-Ru Chan, Samiksha Deme, Paul A Oliphint, Jonghwan Kim, Patrick Allard, Xiaolu A Cambronne","doi":"10.1093/stmcls/sxaf081","DOIUrl":"10.1093/stmcls/sxaf081","url":null,"abstract":"<p><p>Stem cells use oxidized nicotinamide adenine dinucleotide (NAD+) in distinct subcellular compartments to support self-renewal and to regulate chromatin. There is limited information, however, about the biosynthetic pathways that replenish intracellular NAD+, which is continuously turned over in undifferentiated mouse embryonic stem cells. Establishing specific metabolic inputs for maintaining self-renewal can help direct reprogramming efforts. We used single fluorescent protein biosensors for in situ NAD+ measurements in J1 mouse embryonic stem cells. Sensors and controls were localized to the nucleus, cytoplasm, and mitochondrial compartments. Using a specific inhibitor for nicotinamide salvage, we found that loss of this pathway depleted NAD+ concentrations in all three subcellular compartments in undifferentiated culture conditions. We determined that loss of nicotinamide salvage reduced colony size, extended cell cycle, and resulted in diminished expression of self-renewal markers. Supplementation with precursors in the nicotinamide salvage pathway bypassed the pharmacological block, replenished cytosolic NAD+ levels, and reversed the effects on colony size. Notably, supplementation with deaminated precursors did not replenish intracellular NAD+ levels, suggesting minimal contribution from this pathway at this stage. In support, expression data from multiple mouse and human lines showed that nicotinamide salvage pathway enzyme NAMPT was predominantly expressed at the embryonic stem cell stage compared to the enzymes in other NAD+ biosynthesis pathways. Collectively, the data showed that undifferentiated embryonic stem cells heavily rely on nicotinamide salvage, indicating that this dependency is conserved.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145825450","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}

{"title":"miR-124 orchestrates epicardial-mesenchymal transformation and paracrine cardiomyocyte maturation in epicardial-specific Tcf21-PKR1 knockout mice.","authors":"Himanshu Arora, Martina Vincenzi, Anais Audebrand, Amin Kremic, Carmine Gentile, Laurent Desaubry, Canan G Nebigil","doi":"10.1093/stmcls/sxaf082","DOIUrl":"10.1093/stmcls/sxaf082","url":null,"abstract":"<p><p>During the heart development, epicardial-to-mesenchymal transition (EMT) drives the production of progenitor cell populations that contribute to heart formation; however, the molecular control of EMT and its paracrine effects on cardiomyocytes remain poorly elucidated. Here, we defined a novel PKR1-miR-124-SNAI2 signaling axis that orchestrates EMT and coordinates myocardial maturation. Conditional deletion of the prokineticin receptor (PKR1) in mice Tcf21+ epicardial cells caused embryonic lethality and congenital heart disease-like anomalies, including ventricular rupture, arrhythmia, myocardial fibrosis, and impaired contractility. Transcriptomic profiling revealed marked upregulation of miR-124, concurrent with deregulation of EMT genes and signatures of immature cardiomyocytes. Mechanistically, miR-124 directly targets the 3' untranslated region of SNAI2, suppressing this key EMT regulator, resulting in failed EMT, apoptosis, and fibrosis in the epicardium. Functional rescue through miR-124 inhibition or PKR1 reintroduction restores SNAI2 expression, revives EMT, enhances cell survival, and promotes proper cardiomyocyte maturation. Paracrine effects were substantiated by conditioned media and ex vivo assays, demonstrating that epicardial-derived miR-124 suppressed cardiomyocyte contractility and cardiac maturity gene expression-thereby functionally linking epicardial disruption to myocardial immaturity. These findings establish miR-124 as a critical mediator of epicardial-myocardial communication with PKR1 as its upstream regulator. By integrating epicardial plasticity, myocardial maturation, and ECM homeostasis, our work reveals that targeting the PKR1-miR-124-SNAI2 pathway offers a novel mechanistic framework and potential therapeutic target for preventing or treating congenital heart disease.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145848529","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}

{"title":"Optogenetic activation of TGFβ signaling drives ligand-free chondrogenesis in hESC-derived MSCs.","authors":"Jeongmin Lee, Gabsang Lee, Yohan Oh","doi":"10.1093/stmcls/sxaf083","DOIUrl":"10.1093/stmcls/sxaf083","url":null,"abstract":"<p><p>Optogenetics holds great potential for diverse biological applications, including fundamental research, tissue engineering, and regenerative medicine, by enabling the precise spatial and temporal control of cellular signaling pathways. Transforming growth factor-beta (TGFβ), a multifunctional cytokine, is a critical regulator of cell proliferation, differentiation, and particularly chondrogenesis. Although TGFβ signaling is necessary for effective chondrogenic differentiation, previous studies have primarily relied on recombinant TGFβ ligand supplementation. In this study, we established an advanced optogenetic platform by knocking-in opto-TGFβ receptors in the AAVS1 locus of human embryonic stem cells (hESCs), enabling precise optogenetic activation of endogenous TGFβ signaling. Blue light illumination specifically activated TGFβ signaling, indicated by enhanced SMAD2 phosphorylation. Employing a three-dimensional pellet culture system, we demonstrated that direct optogenetic activation of TGFβ receptors, without exogenous ligand supplementation, is sufficient for robust chondrogenic differentiation of hESC-derived mesenchymal stem cells. The efficiency of optogenetic differentiation was comparable to conventional recombinant TGFβ protein treatment, evidenced by the expression of chondrogenic markers and deposition of cartilage-specific extracellular matrix components, including aggrecan and type II collagen. Our findings directly confirm the sufficiency and critical role of TGFβ receptor activation itself in chondrogenesis. Furthermore, this optogenetic approach provides a theoretical advantage by enabling noninvasive external modulation of TGFβ signaling post-transplantation, potentially facilitating further maturation and functional integration of transplanted chondrocytes. Thus, our results highlight a promising recombinant-protein-free strategy for use in cartilage tissue engineering and regenerative medicine.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145843392","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}