Stem Cell Research & Therapy最新文献

{"title":"The impact of T cell exhaustion in hematopoietic stem cell transplantation.","authors":"Yue Li, Huidong Guo, Yikai Zhang, Jie Chen, Liye Zhong, Xiaojun Huang, Yangqiu Li","doi":"10.1186/s13287-026-05141-y","DOIUrl":"10.1186/s13287-026-05141-y","url":null,"abstract":"<p><p>T cell exhaustion is a hallmark of failure to control cancer and chronic infection. In hematological malignancies, T cell exhaustion not only relates to disease progression but also impacts the outcome of hematopoietic stem cell transplantation (HSCT), which may be due to a low graft-versus-leukemia (GVL) effect and a low anti-virus infection capacity. However, a deeper mechanistic understanding of the impact of T cell exhaustion in HSCT remains to be characterized. In this review, we summarize the characteristics of T cell exhaustion, functional alterations in T cells post-transplantation, the role of T cell exhaustion in post-transplant complications, and related therapeutic strategies.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13579798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148346038","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":"Identification of a long-term surviving human mesenchymal stromal cell subpopulation and implications for recessive dystrophic epidermolysis bullosa treatment.","authors":"Mathilde Bonnet des Claustres, Sonia Gaucher, Francesco Carbone, Juliette Peltzer, Marine Luka, Cécile Masson, Patrick Nitschké, Alain Hovnanian, Matthias Titeux","doi":"10.1186/s13287-026-05101-6","DOIUrl":"10.1186/s13287-026-05101-6","url":null,"abstract":"<p><strong>Background: </strong>Recessive dystrophic epidermolysis bullosa (RDEB) is a severe skin disease caused by loss-of-function pathogenic variants in COL7A1 encoding type VII collagen (C7). Patients with RDEB suffer since birth from skin and mucosal blistering and develop severe local and systemic complications resulting in poor prognosis. Mesenchymal stromal cells (MSCs) have demonstrated their potential to enhance wound healing and reduce skin inflammation in RDEB patients due to their anti-inflammatory properties and capacity to express C7. We aim to optimize in vitro conditioning of human bone marrow-derived MSCs (BM-MSCs) to improve their limited survival following local injection in a murine model.</p><p><strong>Methods: </strong>BM-MSCs from healthy human donors were transduced with a lentiviral vector encoding firefly luciferase and mCherry reporter proteins and then subjected to various culture conditions: monolayer on plastic or spheroid culture, either in hypoxia (5% O₂) or in normoxia (21% O₂). These cells were subsequently injected intradermally (ID) in immunodeficient mice and their survival was assessed by in vivo imaging. BM-MSCs populations were analyzed prior to injection by single-cell RNA sequencing (scRNAseq). Murine skin injected with BM-MSCs were sampled two months post-injection and the surviving subpopulations were characterized by spatial transcriptomic.</p><p><strong>Results: </strong>scRNAseq analysis revealed marked variations between monolayer and spheroid conditions, which were significantly impacted by oxygen level. Although most injected cells gradually died within the first 2 months in all tested conditions, 1% of live bioluminescent cells persisted for 54 up to 61 weeks post-injection. Spatial transcriptomics data analysis demonstrated that all surviving cells, regardless of their in vitro preconditioning, retained the expression of the MSC markers THY1, ENG, and NT5E, shared features with fibroblasts, and exhibited enriched expression in genes related to extracellular matrix and collagen fibril organization, which are key processes in wound healing. Spatial transcriptomic and scRNAseq data integration suggested that surviving BM-MSCs were initially present in the injected population, regardless of their culture condition. Remarkably, none of the in vitro preconditioning strategies appeared to affect their survival capacity or functional properties following local injection.</p><p><strong>Conclusions: </strong>The identification and characterization of a BM-MSC subpopulation capable of long-term survival following ID injection hold promise for the development of improved cell therapy protocols for RDEB.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13579746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148340340","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":"Cardiac organoids in toxicology: from construction strategies and research trends to precision screening applications.","authors":"Liya Qiao, Yabing Xu, Xinyu Wang, Yue Zhu, Tianyi Zhang, Yiru Niu, Meng Chen, Sheng Yang, Geyu Liang","doi":"10.1186/s13287-026-05114-1","DOIUrl":"10.1186/s13287-026-05114-1","url":null,"abstract":"<p><p>Cardiovascular diseases (CVDs) are the leading cause of death worldwide, with significant attention focused on the development of therapeutic drugs and research into pathogenic mechanisms. In the real world, cardiotoxicity induced by multiple factors commonly exists and is closely associated with cardiovascular diseases. Traditional toxicity testing models (such as animal experiments and two-dimensional cell cultures) have limited clinical translation value due to species differences, inability to simulate the complex microenvironment of the human body, and cellular interactions. Cardiac organoids, as an emerging three-dimensional (3D) culture platform, possess 3D structure, multicellular composition, organ-specific functions, and self-organizing capabilities, which can highly mimic the physiological and pathological characteristics of the heart, providing a more precise humanized model for the study of cardiovascular disease mechanisms, drug development, and toxicity assessment. This paper systematically reviews the construction strategies of cardiac organoids and their application progress in toxicology: Firstly, it explores the construction standards and technical optimization of cardiac organoids, focusing on human-engineered heart tissue (hEHT) models and various cardiac organoid models that mimic the human heart, with particular attention to their unique characteristics, utility, and limitations. Secondly, through bibliometric analysis using CiteSpace, it reveals research hotspots and trends in cardiac organoid applications for toxicology, specifically by extracting collaboration networks, conducting co-citation analysis, and co-occurrence analysis. Finally, it summarizes specific applications of cardiac organoids in toxicology, including drug toxicity assessment, environmental pollutant toxicity evaluation, cardiac developmental toxicity studies, disease model construction, and multi-organ cascade studies for systemic toxicity assessment.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13579991/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148340371","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":"Dexamethasone reduces osteogenic potential through suppressing retinoic acid signaling via NF-κB/CYP26B1 axis in mesenchymal stem cells.","authors":"Ai-Hua Ye, Yu-Mei Wang, Xin-Yue Wan, Jia Liu, Ni Tang, Wen-Ting Liu, Jie Cai, Dong-Mei He, Bai-Cheng He, Wen-Ge He, Liang Chen","doi":"10.1186/s13287-026-05131-0","DOIUrl":"10.1186/s13287-026-05131-0","url":null,"abstract":"<p><strong>Objective: </strong>Glucocorticoid-induced osteoporosis (GIOP) is the most common secondary osteoporosis, which characterized by the decreased bone strength and increased fracture risk. But the pathogenic causes of GIOP remains not completely yet. In this study, we investigated the effect of Cyp26b1, a key enzyme for all-trans retinoic acid (ATRA) degradation, on the osteogenic inhibitory effect of dexamethasone (DEX) in mesenchymal stem cells (MSCs) and revealed the possible mechanism through which DEX regulates the expression of Cyp26b1.</p><p><strong>Methods: </strong>MSCs were induced with osteogenic induction medium in vitro to establish the osteogenic model, and high concentration (10^- 6 M) of DEX was utilized to treat MSCs to exert its osteogenic inhibitory effect. ATRA content was detected with ELISA, real-time polymerase chain reaction (RT-PCR), western blot, and immunofluorescence staining were employed to detect hall markers for osteogenic differentiation. Chromatin immunoprecipitation (ChIP) assay was used to detect the binding of promoter region of target gene. The rat GIOP model was constructed by intraperitoneal injection of DEX, and the adeno-associated virus was injected via tail vein after the model was constructed. The bone samples were subjected with µ-CT scanning, H&E, and Masson trichrome staining, respectively.</p><p><strong>Results: </strong>DEX (10^- 6 M) decreased the levels of osteogenic markers induced by osteogenic induction medium (OIM) in MSCs, and it was almost reversed by ATRA. But this effect of ATRA was obviously eliminated by overexpression of Cyp26b1. The mRNA expression level of Cyp26b1 was significantly increased by DEX (10^- 6 M), and the content of retinoic acid was decreased in cells. Osteogenic markers decreased by DEX (10^- 6 M) were recovered by Cyp26b1 knockdown, whereas Cyp26b1 overexpression exerted the opposite effect. DEX (10^- 6 M) increased the activation of NF-κB signaling, and the osteogenic inhibitory effects of DEX were ameliorated by NF-κB inhibitors which was almost abolished by Cyp26b1 overexpression. The mRNA level of Cyp26b1 was up-regulated by DEX (10^- 8 M and 10^- 6 M), but the degradation of Cyp26b1 was promoted by DEX (10^- 8 M) only via the lysosomal pathway.</p><p><strong>Conclusion: </strong>The osteogenic inhibitory effect of high concentration of DEX may be resulted from the disturbance of retinoic acid signaling. The expression of Cyp26b1 can be up-regulated by either low or high concentration of DEX, but its degradation can only be inhibited by high concentration of DEX. The effect of DEX on Cyp26b1 expression was partially mediated by activating NF-κB signaling in MSCs.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13579854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148340327","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":"Mesenchymal stem cell-derived microvesicles confer protection against rheumatoid arthritis-associated interstitial lung disease.","authors":"Xiuping Liang, Yanhong Li, Ziyi Tang, Qiuping Zhang, Chunyu Tan, Tong Wu, Deying Huang, Yinlan Wu, Lu Cheng, Yubin Luo, Yi Liu","doi":"10.1186/s13287-026-05119-w","DOIUrl":"10.1186/s13287-026-05119-w","url":null,"abstract":"<p><strong>Background: </strong>Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a serious condition with few treatment options and a poor outlook. Mesenchymal stem cell-derived microvesicles (MSC-MVs) offer a potential cell-free therapy, but their effectiveness and the role of their miRNA content in RA-ILD are not well understood.</p><p><strong>Methods: </strong>A mouse model of comorbid RA-ILD was created using collagen-induced arthritis and bleomycin-induced pulmonary fibrosis. Mice received high- or low-dose MSC-MVs via tail vein injection. The treatment effectiveness was evaluated by assessing arthritis severity and pulmonary fibrosis through clinical scores, imaging, histopathology, lung function, and lung coefficients. The expression of fibrotic markers in the lungs was measured using immunohistochemistry and Western blotting. Small RNA sequencing of MSCs-MVs was conducted to explore the underlying mechanism.</p><p><strong>Results: </strong>Administering MSCs-MVs significantly reduced the severity of arthritis and pulmonary fibrosis. Treated mice had better joint and lung scores, with decreased fibrotic areas and lower levels of fibrotic proteins such as anti-α-smooth muscle actin, collagen I, and fibronectin. Small RNA sequencing revealed that MSC-MVs contain microRNAs (miRNAs) (e.g., miR-148a-3p) that target critical pathways in RA-ILD, such as transforming growth factor-β (TGF-β) and Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling.</p><p><strong>Conclusions: </strong>Our research revealed that MSCs-MVs significantly protect against RA-ILD in a comorbid model. This protective effect is likely facilitated by the transfer of specific miRNAs that modulate essential profibrotic and inflammatory pathways. These results underscore the therapeutic potential of MSC-MVs as an innovative cell-free approach for RA-ILD treatment and identify miRNA-mediated pathway regulation as a pivotal mechanism.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13670665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148333344","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":"Pathological mechanisms and therapeutic potential of MSC-Exos in ischemic stroke management.","authors":"Xiaoming Wei, Zhenwang Zhang, Wanting Han, Wangxianyu Du, Zitong Li, Jiajia Deng, Qing Yang, Tie Peng, Dan Zhu","doi":"10.1186/s13287-026-05120-3","DOIUrl":"10.1186/s13287-026-05120-3","url":null,"abstract":"<p><p>Cerebral ischemia-reperfusion injury (CIRI) represents a critical pathological challenge in the management of ischemic stroke, substantially limiting the clinical efficacy and success rates of neurosurgical interventions, brain tissue therapies, and cell transplantation strategies. The complex pathological mechanisms underlying CIRI, which include inflammatory responses, oxidative stress, ferroptosis, apoptosis, and blood-brain barrier disruption, significantly hinder neurological recovery. Mesenchymal stem cells-derived exosomes (MSC-Exos) have emerged as a promising acellular therapeutic strategy owing to their low immunogenicity, ability to cross the blood-brain barrier, and multi-target regulatory properties. This review compares MSC-Exos derived from multiple sources and summarises their mechanisms of action and therapeutic potential in CIRI. Despite ongoing challenges in standardisation and safety evaluation, accumulating preclinical evidence highlights their potential for future clinical translation and precision regenerative medicine.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13637383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148333326","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":"Exosomal miR-181d-5p derived from distal airway stem cells inhibit apoptosis of pulmonary vascular endothelial cells in COPD mice by targeting PDAP1.","authors":"Qing Song, Cong Liu, Ling Lin, Aiyuan Zhou, Tao Li, Ping Zhang, Yuqin Zeng, Ping Chen","doi":"10.1186/s13287-026-05118-x","DOIUrl":"10.1186/s13287-026-05118-x","url":null,"abstract":"<p><strong>Background: </strong>This study was to investigate the role of exosomes derived from distal airway stem cells (DASC) in apoptosis of pulmonary vascular endothelial cells (PVEC) in chronic obstructive pulmonary disease (COPD) and to explore the potential mechanisms.</p><p><strong>Methods: </strong>Cigarette smoke extract (CSE) plus cigarette smoke (CS)-induced COPD mice were treated with DASC and exosomes. The microRNA (miR) sequencing of exosomes was performed to explore the underlying mechanisms. We determined the expression of miR-181d-5p and PDAP1 in patients with COPD.</p><p><strong>Results: </strong>Compared with control mice, DASC and exosomes derived from DASC could alleviate emphysema changes, decrease the mean linear intercept and alveolar destructive index, reduce apoptosis of PVEC in COPD mice. Furthermore, miR-181d-5p was significantly decreased in exosomes derived from COPD mice DASC when compared with exosomes derived from normal mice DASC. The knockdown of miR-181d-5p in exosomes derived from DASC could weaken its effects in alleviating emphysema and apoptosis of PVEC, increase the expression of PDAP1, and decrease the expression of miR-181d-5p. The overexpression of miR-181d-5p and knockdown of PDAP1 could significantly reduce apoptosis in CSE-induced PVEC. Furthermore, the overexpression of PDAP1 could reverse the anti-apoptotic effect of miR-181d-5p on CSE-induced PVEC. Finally, the expression of miR-181d-5p was decreased in patients with COPD and positively related to pulmonary function, while the expression of PDAP1 was increased and negatively related to pulmonary function.</p><p><strong>Conclusions: </strong>Exosomes derived from DASC could alleviate lung injury in COPD. The mechanism may be to reduce the apoptosis of PVEC by delivering miR-181d-5p by targeting PDAP1.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13560354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148333265","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":"Endothelial-immune cells-on-chip for multiplex evaluation of drug responses through patient plasma screening.","authors":"Khang Leng Lee, Hannah Su-Ann Wee, Zi Yi Teng, Hui Min Tay, Ying Jie Chee, Eunice Xiang Xuan Tan, Yock Young Dan, Mark D Muthiah, Rinkoo Dalan, Han Wei Hou, Christine Cheung","doi":"10.1186/s13287-026-05130-1","DOIUrl":"10.1186/s13287-026-05130-1","url":null,"abstract":"<p><p>Most organ-on-chip models focus on parenchymal cell function, overlooking the critical role of endothelial-immune interactions in metabolic disease pathophysiology. Drugs for metabolic conditions, such as SGLT2 inhibitors, provide not only metabolic improvements but also vascular-protective effects, underscoring the need for human platforms that capture immunovascular dynamics. Here, we developed a human endothelial-immune cells-on-chip system integrating patient-derived blood outgrowth endothelial cells, T cells, and hepatocytes to model the liver sinusoidal microenvironment. Using plasma from type 2 diabetes patients treated with dapagliflozin, the platform revealed reduced endothelial inflammatory activation, attenuated T cell migration, and decreased hepatocyte lipid accumulation, indicating systemic modulation of vascular and hepatic phenotypes. Despite the presence of endothelial SGLT2 protein expression, glucose uptake in vitro was unaltered by dapagliflozin, suggesting these beneficial effects might occur indirectly via plasma factors. Our multiplexed, human-relevant cellular platform enables simultaneous assessment of endothelial, immune, and hepatic responses, offering a versatile tool for personalized plasma-based drug screening and preclinical evaluation of vascular-protective therapies in metabolic diseases.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13560122/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148333276","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":"Recent advances on anti-scarring properties of amniotic membrane: emerging strategies and clinical potentials in regenerative medicine.","authors":"Kiarash Soltani, Farnaz Niknejad, Shayan Sadrinasab, Yasaman Gholinezhad, Radman Mazloomnejad, Tahereh Tayebi, Hassan Niknejad","doi":"10.1186/s13287-026-05126-x","DOIUrl":"10.1186/s13287-026-05126-x","url":null,"abstract":"<p><p>Scarring remains an inevitable consequence of adult wound healing, often accompanied by functional, aesthetic, and psychological burdens. In contrast, fetal wound healing follows a fundamentally different trajectory, characterized by minimal inflammation, abundant hyaluronic acid, elevated type III collagen, and balanced matrix remodeling, culminating in regeneration without scar formation. This regenerative capacity is largely absent in adult tissues, which is the main incentive for understanding the pathophysiology of scarless healing phenotype to replicate such outcomes in adult tissues. The human amniotic membrane (hAM), as an embryogenic derivative, shares many structural and biochemical properties with fetal cutaneous tissue, positioning it as a promising biological tool to bridge adult wound healing toward a scarless, fetal-like outcome. hAM contains a rich milieu of growth factors, anti-inflammatory cytokines, and extracellular matrix components that support epithelialization, angiogenesis regulation, fibroblast modulation, and myofibroblast suppression. These effects are mediated through modulation of key signaling pathways including TGF-β/SMAD, PI3K/AKT, Wnt/β-catenin, and MAPK cascades; each central to the orchestration of fibrosis and regeneration. Furthermore, hAM's angio-modulatory behavior, antioxidant capacity, and context-dependent immune regulation contribute to a healing microenvironment that more closely mimics fetal conditions. In this review, we highlight the unique biology of fetal scarless healing which can be harnessed through the use of amniotic membrane-based therapies in adults. We highlight how the properties of hAM can help shift adult wound healing toward a more regenerative, less fibrotic outcome. We also examine different ways hAM is processed and applied in clinical settings and processing effects on anti-scar characteristic of hAM and discuss the main challenges that still need to be addressed, such as product standardization and optimizing treatment protocols, in a biomimetic way from scarless wound healing in embryo. Altogether, application of hAM presents a compelling and biologically sound approach to promote scarless wound healing in adult patients, a longstanding goal in regenerative medicine.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13560457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148318969","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":"A 3D-printed extravascular stent containing sirtuin-3 engineered human bone marrow mesenchymal stem cells maintains venous graft patency.","authors":"Kexun Liu, Xin Sun, Xuan Jiao, Limeng Chao, Bohao Zhang, Chang Liu, Jie Wu, Mingli Huang, Peian Cai, Xin Li, Yuanzhong Zhao, Xin Tian, Ren-Ke Li, Wei Chen, Hai Tian","doi":"10.1186/s13287-026-05127-w","DOIUrl":"10.1186/s13287-026-05127-w","url":null,"abstract":"<p><strong>Background: </strong>Coronary artery bypass grafting (CABG) reconstructs the blood supply for treating coronary heart disease. One of the most used conduits is the great saphenous vein, but its effect is limited, owing to lower long-term patency versus arterial grafts. This study devised a 3D bio-printed stent, comprising of genetically modified human bone marrow mesenchymal stem cells (BMSCs), to improve venous graft patency.</p><p><strong>Methods: </strong>BMSCs and endothelial cells (ECs) were obtained from sternal bone marrow and discarded saphenous veins, respectively. BMSCs were transduced with lentivirus overexpressing sirtuin-3 (SIRT3) and seeded on a 3D bio-printed matrix stent, comprising of hyaluronic acid methacryloyl and gelatin methacryloyl (HAMA/GelMA). A rat CABG model was established, via generating a jugular vein-common carotid artery arteriovenous graft. The SIRT3-BMSC-seeded stent was \"wrapped\" around this venous graft, serving as an extravascular stent. An in vitro model was also devised, in which lipopolysaccharide (LPS)-pre-treated ECs were co-cultured with SIRT3-BMSCs, followed by evaluating mitochondrial transferal and tunneling nanotube (TNT) formation-related functional changes. Immunoprecipitation was used to examine SIRT3-vasodilator-simulated phosphoprotein (VASP) interactions.</p><p><strong>Results: </strong>Rat arteriovenous graft model found that SIRT3-BMSC+stent, compared to Control, Stent, and BMSC+stent groups, had the greatest graft vessel diameter, maximum blood flow velocity during systole and CD31⁺ EC area, along with the lowest cell proliferation and inflammatory cell infiltration; therefore, SIRT3-BMSC+stent had the greatest inhibitory effects on venous graft neointimal formation. In vitro, LPS-pre-treated ECs, after co-culture with SIRT3-BMSCs, restored endothelial, along with lowering mesenchymal marker expression. Furthermore, mechanistic analyses revealed increased SIRT-BMSC-to-LPS-pre-treated EC mitochondrial transfer, facilitated by TNTs formed between SIRT3-BMSCs and ECs. This mitochondrial transfer was mediated via SIRT3-VASP interactions, in which SIRT3 deacetylates VASP to promote TNT.</p><p><strong>Conclusion: </strong>SIRT3-BMSC/HAMA/GelMA extravascular stent could effectively lower arteriovenous graft dilation and inhibit neointimal formation, possibly via SIRT3 deacetylation of VASP, thereby promoting TNT formation, and subsequently, mitochondrial transfer from BMSCs to ECs to improve EC function. Thus, the extravascular stent was able to provide external support, along with facilitating BMSC therapeutic effects.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13560131/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148333323","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}