Stem Cell Research & Therapy最新文献

{"title":"Nanofiber-reinforced ECM-based bioink for hybrid biofabrication of adventitia-mimetic anisotropic vascular constructs.","authors":"Zhiyuan She, Yingqian Zhou, Shan Mou","doi":"10.1186/s13287-026-05168-1","DOIUrl":"10.1186/s13287-026-05168-1","url":null,"abstract":"<p><strong>Background: </strong>Tissue-engineered blood vessels are essential for vascular grafting. Despite significant progress, current research predominantly focuses on the macroscopic scale of vascular grafts, neglecting the anisotropic microstructure of the vascular wall, particularly the adventitia, which plays a key role in the mechanical stability and functional performance of native vessels. Consequently, this aspect remains underexplored in current vascular tissue engineering strategies, limiting the full potential of vascular graft development.</p><p><strong>Methods: </strong>In this study, we developed a novel hybrid biofabrication strategy combining electrospinning and coaxial extrusion printing with nanofiber-reinforced bioinks to fabricate vascular constructs that mimic the anisotropic structure of the vessel wall. The bioink, composed of a gelatin methacryloyl hydrogel matrix, contains short electrospun polycaprolactone fibers and vascular-derived extracellular matrix, which improve the mechanical stability, printability, and biocompatibility of the bioink while also providing micro/nano-scale structure.</p><p><strong>Results: </strong>Using coaxial extrusion printing, we successfully fabricated vascular constructs with well-aligned fibers and cells oriented along the long axis of the artificial vessel, mimicking the micro-/nano-architecture of the adventitia. Finite element analysis revealed that shear stress during extrusion induced fiber and cell alignment, creating anisotropic structures that enhance the potential for vascular tissue engineering applications. In vivo studies demonstrated that these constructs promote host integration and vascular ingrowth without causing excessive inflammation.</p><p><strong>Conclusions: </strong>A promising strategy for fabricating vascular grafts with biomimetic adventitia-like structures is presented in this study, thereby providing a versatile platform for engineering vascular and other anisotropic tissues.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13644084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148424251","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 cells reverse ovarian dysfunction by inhibiting autophagy in polycystic ovary syndrome mice.","authors":"Qiwei Liu, Lei Zhan, Liang Kong, Yuanyuan Ma, Jinjuan Wang, Junhui Zhang","doi":"10.1186/s13287-026-05162-7","DOIUrl":"10.1186/s13287-026-05162-7","url":null,"abstract":"<p><strong>Background: </strong>Polycystic ovary syndrome (PCOS) is a chronic inflammatory disorder that affects the reproductive health of 5%-18% of women of reproductive age worldwide. However, PCOS is yet to be completely cured. As a biomaterial that regulates the conditions of the female reproductive system, many studies have demonstrated that mesenchymal stromal cells (MSCs) have significant therapeutic potential for restoring impaired ovarian function. The purpose of the study was to examine the therapeutic benefits of human umbilical cord mesenchymal stromal cells (Huc-MSCs) in mice with dehydroepiandrosterone (DHEA)-induced PCOS and to assess their effects on ovulation, sex hormones, and the estrous cycle.</p><p><strong>Methods: </strong>Flow cytometry (FCM) was used to identify Huc-MSCs. The expression of the autophagy-related proteins LC3 II, Beclin1, and mammalian target of rapamycin (mTOR) was evaluated by Western blot (WB) and real-time quantitative polymerase chain reaction (RT-qPCR). Changes in the number of autophagosomes were assessed by transmission electron microscope (TEM). DHEA was subcutaneously injected into female C57BL/6J mice to develop a PCOS model. The morphological changes in the ovaries and the number of oocytes at various stages of development in PCOS mice were observed using hematoxylin and eosin (H&E) staining. The levels of sex hormones were measured using enzyme-linked immunosorbent assay (ELISA), and the estrous cycle of PCOS mice was monitored using vaginal smears.</p><p><strong>Results: </strong>The PCOS patient group exhibited significantly higher levels of ATG5 and Parkin than the control group and a significant increase in the number of autophagosomes in the GCs of PCOS patients compared with those of non-PCOS women. Huc-MSCs are capable of repairing the impaired estrous cycle in PCOS mice and decreasing the level of testosterone (T) and the ratio of luteinizing hormone (LH)/ follicle-stimulating hormone (FSH) (LH/FSH ratio). Huc-MSCs are also able to repair ovulatory functions and facilitate oocytes maturation in PCOS mice. Autophagy suppression can improve oocytes viability in mice. Huc-MSCs also can inhibit granulosa cell autophagy, promote oocytes development, maintain homeostatic hormone levels, and restore the estrous cycle in PCOS mice. Huc-MSCs have the potential to treat ovarian dysfunction in PCOS mice by inhibiting autophagy pathway. In KGN cells and in DHEA-induced PCOS mice, mTOR expression was significantly downregulated. Huc-MSCs treatment markedly upregulated mTOR levels.</p><p><strong>Conclusions: </strong>Our results suggest that Huc-MSCs improve ovarian dysfunction in PCOS by inhibiting autophagy, providing experimental evidence for the clinical application of hUC-MSCs and offering a new therapeutic approach for the treatment of PCOS.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148424230","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":"Obesity and diabetes associated with dysregulation of mevalonate pathway markers and progression from pancreatic intraepithelial neoplasia to invasive pancreatic tumor.","authors":"Fereshteh Rezagholizadeh, Sara Rokn, Mohammadhossein FakherBaheri, Zahra Taherian, Hossein Rostami, Farid Azmoudeh-Ardalan, Mandana Rahimi, Masoud Baghai Wadji, Atefeh Kashanizadeh, Sanaz Eghtedari, Alireza Lotfalizadeh, Ali Sharifi-Zarchi, Elahe Safari, Mohammad Taghi Joghataei","doi":"10.1186/s13287-026-05158-3","DOIUrl":"10.1186/s13287-026-05158-3","url":null,"abstract":"<p><strong>Background: </strong>Cholesterol metabolic reprogramming plays a key role in pancreatic cancer progression by regulating the tumor immune microenvironment (TIME) and influencing responses to immunotherapy. Pancreatic intraepithelial neoplasia (PanIN) is the most common precursor lesion of pancreatic ductal adenocarcinoma (PDAC), a malignancy that commonly occurs in individuals with high BMI and type 2 diabetes mellitus (T2DM). Key metabolic markers (SOAT1 and SREBP2), the tumor suppressor P53, and the immune marker CD8 are implicated in PanIN initiation, PDAC progression, and subsequent metastasis, but their associations-particularly for those that are potentially targetable-remain poorly defined.</p><p><strong>Methods: </strong>Using publicly available PDAC datasets from the GEO database, we conducted in silico analyses to investigate the genes of interest. Additionally, we used laser capture microdissection to isolate specific cells from pancreatic cancer tissues obtained from patients. We performed translational research using 17 tumor samples, as well as 17 microdissected PanIN lesions and matched normal tissues. Protein expression analysis was further conducted on a larger cohort, including 65 PanIN lesions and 157 tumor tissues from PDAC patients.</p><p><strong>Results: </strong>Our data identify a dual-direction expression pattern in obese and diabetic patients, with elevated levels of SOAT1, SREBP2, and P53, and reduced CD8 expression, suggesting a coordinated metabolic and immunological alteration in pancreatic cancer. High BMI and T2DM, recognized as independent risk factors for PDAC, are significantly associated with dysregulation of key markers involved in the mevalonate pathway and the TIME, potentially contributing to PanIN and PDAC progression.</p><p><strong>Conclusion: </strong>These findings warrant further longitudinal and mechanistic studies to clarify whether metabolic modulation may influence PDAC risk or clinical outcomes.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13644116/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148424218","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":"Allogeneic mesenchymal stromal cells ameliorate lupus nephritis by regulating lipid metabolism via ASGR1.","authors":"Yujiao Wang, Ling Zhao, Simin Guo, Yirui Shi, Yue Zhang, Xiaojuan Han, Xiaojun Tang, Genhong Yao, Weiwei Chen, Lingyun Sun","doi":"10.1186/s13287-026-05167-2","DOIUrl":"10.1186/s13287-026-05167-2","url":null,"abstract":"<p><strong>Background: </strong>Systemic lupus erythematosus (SLE) is an autoimmune disease in which disruptions in lipid metabolism contribute to immune dysregulation, inflammation, and organ damage. This study aims to elucidate the role of hepatic asialoglycoprotein receptor 1 (ASGR1) in lipid metabolism dysregulation in lupus nephritis, and to investigate the therapeutic potential of mesenchymal stromal cells (MSCs) in restoring lipid homeostasis via ASGR1 modulation.</p><p><strong>Method: </strong>A high-fat diet (HFD)-fed MRL/lpr lupus mouse model was used to assess the impact of lipid dysregulation on lupus pathology. ASGR1 expression and cholesterol metabolism-related genes were evaluated using molecular and histological analyses. Liver-specific Asgr1 knockdown was achieved using adeno-associated virus. The therapeutic effects of MSCs were evaluated both in vivo and in vitro, with a focus on ASGR1 regulation and downstream metabolic signaling.</p><p><strong>Results: </strong>In MRL/lpr mice, HFD exacerbated lipid accumulation, renal injury, and immune imbalance. ASGR1 expression was significantly upregulated in the liver, leading to suppressed cholesterol efflux and enhanced lipid synthesis. Asgr1 knockdown ameliorated these metabolic disturbances. MSCs treatment reduced ASGR1 expression, restored lipid homeostasis, and improved lupus phenotypes by modulating mTOR, LXRα, and AMPK pathways. Overexpression of Asgr1 reversed the protective effects of MSCs in vitro.</p><p><strong>Conclusions: </strong>Lipid metabolism dysregulation contributes to SLE pathogenesis through ASGR1-mediated pathways. Targeting ASGR1, particularly via MSCs therapy, offers a promising strategy to restore metabolic balance and attenuate disease severity in lupus nephritis.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13637109/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148424256","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":"Safety and preliminary efficacy of autologous bone marrow-derived mesenchymal stem cell transplantation in hereditary cerebellar ataxia: phase I/IIa clinical trial.","authors":"Abbas Shapouri Moghaddam, Jalil Tavakol-Afshari, Najmeh Kaffash Farkhad, Majid Mojarrad, Maryam Eslami, Shahram Savad, Mohammad Ali Khodadoust, Ala Orafaie, Mohammadreza Sobhani, Akram Farmanbar, Mohammad Dashtkoohi, Hamid Khodayari, Delaram Hassani, Shahrzad Najafi, Parizad Najafi, Jürgen Hescheler, Karim Nayernia, Amirreza Boroumand","doi":"10.1186/s13287-026-05163-6","DOIUrl":"10.1186/s13287-026-05163-6","url":null,"abstract":"<p><strong>Background: </strong>Hereditary cerebellar ataxias (HCA) encompass a spectrum of pathological conditions affecting the cerebellum. Currently, there is growing interest in the potential role of mesenchymal stem cells (MSCs) as an investigational therapeutic approach for this condition. Hence, the objective of this single-center, open-label, phase I/IIa clinical trial was to assess the safety and exploratory clinical and biomarker changes following a single intrathecal injection of autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) in HCA.</p><p><strong>Methods: </strong>Ten confirmed patients with HCA entered the study and underwent a single dose of (1 × 10⁶ cells/kg BW) intrathecal transplantation of BM-MSCs at passage 3. During the follow-up, patients were evaluated four times (one month before the intervention (-1), months 1, 3, and 6). Assessments included safety evaluation, Scale for the Assessment and Rating of Ataxia (SARA), GAD 65-antibody, and specific cytokines in the patient's serum and cerebrospinal fluid (CSF) samples.</p><p><strong>Results: </strong>No severe adverse effects were observed following the cell transplantation procedure. A decreasing trend in SARA score was observed, with a statistically significant difference at month 6 compared with baseline. Except for one patient, GAD-65 antibody levels remained within the normal range in all patients. In one patient with markedly elevated baseline GAD-65 titers, serum and CSF GAD-65 levels decreased from 814 IU/mL and 781 IU/mL, respectively, to values within the normal range after 3 months. Significant changes were observed in selected inflammatory biomarkers, including decreased serum IL-6 at month 3, decreased CSF TNF-alpha at months 1 and 3, and increased serum IL-10 during follow-up. CSF IL-6 did not show a significant decrease.</p><p><strong>Conclusion: </strong>The findings support the short-term safety and tolerability of a single intrathecal dose of autologous BM-MSCs in this small HCA cohort. The study provides preliminary signals of possible clinical and biomarker changes; however, efficacy cannot be established due to the uncontrolled design, small sample size, disease heterogeneity, and short follow-up. Larger randomized controlled trials are required to validate these exploratory findings.</p><p><strong>Trial registration: </strong>This clinical trial was registered with the Iranian Registry of Clinical Trials (ID: IRCT20160809029275N3).</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"17 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13352641/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148424275","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":"Extracellular vesicles derived from engineered BMSCs improve damaged cartilage in mice with osteoarthritis by delivering PBX1.","authors":"Yunqi Zhang, Fusen Wang, Huan Yu, Changqing Jiang, Zhong Li, Rongqiang Bu, Jun Yu","doi":"10.1186/s13287-026-05152-9","DOIUrl":"10.1186/s13287-026-05152-9","url":null,"abstract":"<p><strong>Background: </strong>The beneficial effects of bone marrow mesenchymal stem cells (BMSCs) have been linked to their secreted extracellular vesicles (EVs). These EVs can suppress cartilage degradation and prevent apoptosis in articular cells. We aimed to explore the therapeutic efficacy of engineered BMSCs-EVs in the treatment of osteoarthritis (OA).</p><p><strong>Methods: </strong>The isolation of BMSC-derived EVs was conducted via ultracentrifugation techniques, followed by characterization. Engineered EVs were obtained by transfecting chondrocyte-affinity peptide (CAP) and Pre-B-cell leukemia transcription factor 1 (PBX1) expression plasmids into BMSCs. OA injury was induced by the treatment of chondrocytes with IL-1β, and the OA mouse model was established by DMM surgery. The efficacy of different EVs was examined in vitro and in vivo. EVs treatment and combined genetic interventions were performed in vitro and in vivo.</p><p><strong>Results: </strong>Both CAP modification and increased protein loading of PBX1 strengthened the protective effect of EVs on chondrocytes and ameliorated OA-induced cartilage damage. PBX1 promoted extracellular signal-regulated kinase (ERK) signaling and the expression of the downstream molecule c-FOS in chondrocytes by activating the transcriptional expression of calcium channel voltage-dependent subunit beta 4 (CACNB4). The chondroprotective effect of engineered EVs was significantly attenuated by inhibiting CACNB4/ERK signaling in IL-1β-treated chondrocytes, as well as in the DMM-induced mouse model.</p><p><strong>Conclusion: </strong>Engineering (CAP modification and increased PBX1 protein loading) enhances the therapeutic efficacy of BMSCs-EVs on chondrocytes, which depends on the activation of the CACNB4/ERK signaling. Engineered EVs represent a promising treatment for OA cartilage damage.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13637302/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148424215","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":"Regulatory mechanism of stem cell scaffold porosity and stiffness on the processes of intramembranous ossification and bone regeneration.","authors":"Qianqian Chen, Shichun Xu, Yiqi Su, Sengyang Xiao, Qingchen Meng, Wenjing Li, Yunwei Wang, Dan Xing, Hui Li","doi":"10.1186/s13287-026-05170-7","DOIUrl":"10.1186/s13287-026-05170-7","url":null,"abstract":"<p><p>Bone defects remain a significant clinical challenge due to the limited regenerative capacity. Biomaterials can offer effective therapeutic approaches to address this challenge, where their physical properties play a critical role in determining the success of regeneration. Here, we fabricated cryogelated 3D porous scaffolds with independently controlled pore sizes and stiffness. These scaffolds were then seeded separately with bone marrow stromal cells (BMSCs) and MLO-A5 cells to create osteogenic cell-scaffold composites. To determine the optimal physical properties for promoting bone regeneration, we evaluated the scaffolds using both in vitro osteogenic cultures and a rat critical-sized calvarial defect model. Transcriptomic analysis was performed concurrently to explore the molecular link between physical scaffold cues and osteogenic differentiation. The results indicated that the small-pore high-stiffness scaffold exhibited the optimal osteogenic performance in vitro. In rats, the small pore scaffold groups also showed superior bone regeneration. Furthermore, transcriptomic analysis revealed that scaffold pore size significantly changed the expression of Apolipoprotein E (ApoE) and Osteoglycin (OGN). Our findings suggest a feasible strategy to enhance the efficiency of bone regeneration by leveraging the properties of tailored scaffolds, enabling personalized repair approaches.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148424268","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":"Psoralen enhances direct cardiac reprogramming via activating PPARα and driving mitochondrial fission and improves cardiac function after myocardial infarction.","authors":"Wenjie Li, Haixia Liu, Xinyu Wan, Ding Cheng, Zhiguo Zhang, Ruyuan Zhu","doi":"10.1186/s13287-026-05160-9","DOIUrl":"10.1186/s13287-026-05160-9","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Direct cardiac reprogramming offers a promising strategy to regenerate cardiomyocytes for heart repair, but its efficiency and maturation remain limited. Psoralen, a natural compound isolated from Psoralea corylifolia L., has been widely studied for its bioactive properties. This study aimed to determine whether psoralen enhances chemical cardiac reprogramming and improves functional maturation, and to evaluate its therapeutic potential in myocardial infarction.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Mouse embryonic fibroblasts were treated with a chemical reprogramming cocktail containing RepSox and Forskolin, with or without psoralen. Gene expression was assessed by quantitative PCR and Western blotting. Sarcomere ultrastructure was examined by transmission electron microscopy. Mitochondrial content and morphology were analyzed using MitoTracker staining. Calcium handling was evaluated in Fluo-4 loaded induced cardiomyocytes. Metabolic profiles were measured with Seahorse assays. RNA sequencing and protein-protein interaction analysis were used to identify signaling pathways activated by psoralen. To investigate the functional role of mitochondrial fission in psoralen enhanced reprogramming, the DRP1 inhibitor Mdivi-1 was added to the reprogramming cocktail. An immortalized human skin fibroblast cell line was additionally used to evaluate cardiac marker expression and mitochondrial morphology following treatment with RepSox, Forskolin, and psoralen. For in vivo evaluation, a myocardial infarction model was generated in male C57BL/6J mice, which were subsequently treated for 7 days. Cardiac function was measured by echocardiography, and histological changes were assessed by HE and Masson's trichrome staining.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Psoralen (10 µM) significantly increased the induction efficiency of induced cardiomyocytes, leading to the rapid appearance of beating clusters(day 1 vs. day 6-8) and marked upregulation of cardiac structural genes. Psoralen-treated cells displayed enhanced sarcomere organization, improved calcium transients, and a metabolic shift toward oxidative phosphorylation characterized by higher mitochondrial respiration and reduced glycolysis. Transcriptomic profiling identified activation of the PPAR signaling pathway, with PPARα, RXRG, and UCP1 as central nodes. Psoralen also enhanced mitochondrial fission by upregulating fission-related genes and proteins. Mdivi-1 attenuated psoralen-induced cardiac gene expression and mitochondrial fragmentation. In immortalized human skin fibroblasts, psoralen combined with RepSox and Forskolin increased cardiac marker expression and promoted mitochondrial fragmentation. In vivo, psoralen combined with RepSox and Forskolin enhanced cardiac function and reduced fibrosis after myocardial infarction compared to RepSox and Forskolin alone.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Psoralen enhances chemical direct cardiac reprogramming by activating metabolic and ","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13637282/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148412874","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":"Safety evaluation of repeated administration of umbilical cord mesenchymal stem cell-derived exosomes.","authors":"Ting Lan, Tao-Tao Tang, Jing-Jing Di, Suo-Fu Qin, Aihemaiti Muzaipaier, Qin-Yu Zhou, Bi-Cheng Liu, Qiu-Li Wu","doi":"10.1186/s13287-026-05172-5","DOIUrl":"10.1186/s13287-026-05172-5","url":null,"abstract":"<p><strong>Background: </strong>Mesenchymal stem cell-derived exosomes (MSC-Exos) have shown considerable therapeutic potential in regenerative medicine. However, the biosafety profile of these exosomes following repeated administration has not been adequately characterised, and this knowledge gap continues to hinder clinical translation.</p><p><strong>Methods: </strong>Human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-Exos) were produced on a xeno-free platform by replacing fetal bovine serum (FBS) with human platelet lysate (hPL). A relatively comprehensive and integrated repeated-dose preclinical biosafety profile assessment was then conducted using polyethylene glycol (PEG)-Liposomes as reference nanovesicles. The assessment included pharmacokinetic and distribution analyses using DiD labelling, haematological cytology testing, quantitative measurement of inflammatory cytokines and chemokines, histopathological scoring, and RNA sequencing.</p><p><strong>Results: </strong>In this study, the safety assessment revealed that: (1) hucMSC-Exos primarily accumulated in the liver and spleen and exhibited an approximately 4-h circulation time; (2) repeated intravenous administration of hucMSC-Exos for 30 days did not result in overt systemic inflammation, and the evaluated haematological and biochemical parameters remained within the normal range; (3) RNA sequencing showed that hucMSC-Exos avoided immune pathway activation (e.g., IL-17/antigen presentation) triggered by PEG-Liposomes, instead enriching complement-coagulation cascades (e.g., C1qc, C6 upregulation) and metabolic pathways (steroidogenesis, retinol metabolism). Together, these findings suggest that hucMSC-Exos have a favourable biosafety profile in a murine model and support further preclinical evaluation for regenerative medicine applications.</p><p><strong>Conclusion: </strong>This study suggests that repeated intravenous administration of hucMSC-Exos confers a relatively favourable biosafety profile in a murine model and provides preliminary preclinical evidence for further investigation towards clinical translation.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13637395/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148412215","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":"LGR5 as a therapeutic target for decidualization-based endometrial mesenchymal stem cells therapy in thin endometrium.","authors":"Kai Chen, Xueqing Ning, Huiru Wang, Jingxin Wang, Xin Zhao, Lu Zong, Shengxia Zheng","doi":"10.1186/s13287-026-05173-4","DOIUrl":"10.1186/s13287-026-05173-4","url":null,"abstract":"<p><strong>Background: </strong>Decidualization of endometrial mesenchymal stem cells (ESCs) is crucial for the implantation of the embryo. Thin endometrium (TE) can impair endometrial receptivity by affecting the decidualization of ESCs. However, how TE affects the decidualization of ESCs remains unclear.</p><p><strong>Methods: </strong>Through multiple transcriptome analyses, we found that LGR5 plays a crucial role in the decidualization of ESCs. In vitro, siRNA was used to knock down LGR5 in ESCs, and decidualization was assessed via morphology, qRT-PCR, Western blot, and ELISA for decidualization marker (PRL, IGFBP-1). Colony forming assay, EdU, CFSE, and tube formation were used to evaluate proliferation and secretion. Signaling pathway components (β-catenin, AXIN2, PGR) were analyzed. In vivo, an adeno-associated virus (AAV) delivered shRNA to knock down Lgr5 in mouse uterine to assess endometrial receptivity and pregnancy rates. A TE mouse model was established and treated with decidualized endometrial mesenchymal stem cells (DSCs) or LGR5-knockdown DSCs to evaluate therapeutic efficacy.</p><p><strong>Results: </strong>LGR5 was significantly upregulated during decidualization and downregulated in TE tissues. In vitro, LGR5 knockdown impaired DSCs' morphological transformation, reduced decidualization, restored proliferation, but diminished secretory function and angiogenic potential. Mechanistically, LGR5 knockdown suppressed the β-catenin pathway and downregulated progesterone receptor (PGR). In vivo, Lgr5 knockdown reduced endometrial thickness, receptivity markers (Lif, Hoxa10, Pgr), and embryo implantation numbers. Crucially, transplanting LGR5-knockdown DSCs into TE mice resulted in inferior restoration of endometrial structure, reduced angiogenesis, and lower pregnancy rates compared to DSCs.</p><p><strong>Conclusion: </strong>LGR5 plays an important role in ESCs decidualization and may contribute to the therapeutic efficacy of DSCs for TE repair, potentially through regulation of PGR via the β-catenin pathway. These results indicate that LGR5 represents a candidate target worthy of further investigation for developing function-restoring therapies in TE.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13637238/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148412899","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}