Stem Cell Research & Therapy最新文献

{"title":"Small extracellular vesicles derived from mesenchymal stromal cells loaded with β-nicotinamide mononucleotide activate NAD⁺/SIRT3 signaling pathway-mediated mitochondrial autophagy to delay skin aging.","authors":"Zixuan Sun, Jiali Li, Yuzhou Zheng, Jiaxin Zhang, Wenhuan Bai, Xinyi Deng, Zhijing Wu, XueZhong Xu, Wei Ding, Hui Qian, Yulin Tan","doi":"10.1186/s13287-025-04460-w","DOIUrl":"10.1186/s13287-025-04460-w","url":null,"abstract":"<p><strong>Background: </strong>Recently, the beneficial effects of human umbilical cord mesenchymal stromal cell (hucMSC)-derived small extracellular vesicles (sEVs) in mitigating skin aging through multiple mechanisms have been widely reported. β-Nicotinamide mononucleotide (NMN) is an iconic anti-aging drug that increases NAD⁺ levels in the body to slow down, ameliorate, and prevent various phenotypes associated with aging, but its high water solubility, low permeability, and instability limit its clinical application. Based on this, we applied electroporation to construct NMN-loaded hucMSC-sEVs (NMN-sEVs) to improve their stability and efficacy and to enhance their potential for translational application in medical aesthetics and anti-aging.</p><p><strong>Methods: </strong>D-galactose was applied to construct a mouse skin aging model, based on which comparative analyses of topical and nano-microneedle administration were performed to determine the optimal delivery method of sEVs in vivo experiments. After constructing NMN-sEVs by electroporation, high-performance liquid chromatography was applied to detect the loading efficiency, and the effects of NMN-sEVs on delaying skin aging were assessed by histological analysis. In addition, the defense effects of NMN-sEVs against cellular senescence were verified by reactive oxygen species assay, β-galactosidase staining, qRT-PCR, Western blot, and cellular immunofluorescence. Finally, the roles of NMN-sEVs in remodeling mitochondrial function and delaying cellular senescence through mitochondrial autophagy were assessed by mitochondrial mass, function, and autophagy level assays.</p><p><strong>Results: </strong>Our data suggested that NMN-sEVs could improve skin aging in mice, delay cellular senescence, and restore cellular mitochondrial dysfunction. Notably, NMN-sEVs treatment increased intracellular NAD⁺ levels and SIRT3 expression, as well as rescued the inhibition of senescence-induced mitochondrial autophagy, suggesting a role for NMN-sEVs in the remodeling of mitochondrial function through mitochondrial autophagy. Additionally, the use of the SIRT3 inhibitor 3-TYP suppressed the positive effects of NMN-sEVs on cellular senescence, mitochondrial function, and mitochondrial autophagy while restoring senescence-associated characteristics.</p><p><strong>Conclusion: </strong>Overall, our findings revealed a mechanism by which NMN-sEVs attenuated mitochondrial dysfunction and rescued cellular senescence by promoting NAD⁺/SIRT3 pathway-mediated mitophagy and might provide a promising strategy for anti-aging pharmaceuticals.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"339"},"PeriodicalIF":7.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12218950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144544944","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":"Tensile stress promotes the chondrogenic ability of condylar cartilage stem/progenitor cells in the temporomandibular joint via the Piezo1-Ca²⁺-Prkca pathway.","authors":"Wuyi Gong, Zhihang Yue, Haojun Chu, Xiaohui Mi, Yongming Li","doi":"10.1186/s13287-025-04439-7","DOIUrl":"10.1186/s13287-025-04439-7","url":null,"abstract":"<p><strong>Background: </strong>Tensile force is a key regulator for condylar cartilage remodeling in the temporomandibular joint (TMJ), and this biomechanical characteristic underlies the mechanisms of mandibular growth modification in orthodontic practice. Cartilage stem/progenitor cells (CSPCs) in the superficial layer of condylar cartilage play an essential part in the development and remodeling of condylar cartilage. However, the regulatory role of tensile force on condylar CSPCs remains unclear. This study aimed to investigate the impact of tensile loading on condylar CSPCs and explore the molecular mechanisms within.</p><p><strong>Methods: </strong>The mandibular advancement (MA) model was constructed to apply tensile force on the condylar cartilage in vivo. Flow cytometry and transcriptome sequencing were utilized to assess the percentage of CSPCs and gene expression in the superficial layer of rat condylar cartilage. Lineage tracing with cathepsin K (Ctsk) in mice was employed to trace the differentiation of CSPCs. 10% equibiaxial dynamic strain was loaded on rat CSPCs for cell stretching in vitro. GsMTx4 was used to inhibit the Piezo1 channel, and the calcium chelating agent BAPTA was used to block the Ca²⁺ influx of rat CSPCs. siRNA was applied to knock down the protein kinase C alpha (Prkca) of rat CSPCs in vitro and in vivo.</p><p><strong>Results: </strong>Cartilage thickening and a transient reduction of the CSPCs proportion in the superficial layer of the condylar cartilage were observed after 1 week of MA. The ratio of Ctsk and type II collagen double-positive cells climbed in the first week after MA, and 2 weeks later, the ratio of Ctsk and EdU double-positive cells rose. The expression level of chondrogenic-related genes, Piezo1, and Prkca was elevated in CSPCs after tensile loading. GsMTx4 and BAPTA could block the Ca²⁺ influx into CSPCs caused by tensile stress. Furthermore, BAPTA and siPrkca could inhibit the stretch-induced chondrogenesis of CSPCs.</p><p><strong>Conclusions: </strong>We uncovered that tensile stress could cause a transient shrinkage of the CSPCs pool in condylar cartilage, resulting from the accelerated chondrogenesis of CSPCs. Tensile force could promote the chondrogenic ability of CSPCs via the Piezo1-Ca²⁺-Prkca pathway. This study suggested a new regulatory route for mandibular growth modification in orthodontic practice.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"331"},"PeriodicalIF":7.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12210528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144544945","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":"Salvage treatment of steroid-refractory acute GVHD with the off-the-shelf product of human umbilical cord mesenchymal stromal cells: a multicenter, open label, phase Ib/IIa trial.","authors":"Yanmin Zhao, Yi Luo, Jimin Shi, Jian Yu, Lizhen Liu, Xiaoyu Lai, Huarui Fu, Yeqian Zhao, Yi Yu, Yishan Ye, Congxiao Zhang, Nainong Li, Erlie Jiang, Qiong Xie, Jundong Gu, Zhibo Han, Zhongchao Han, He Huang","doi":"10.1186/s13287-025-04446-8","DOIUrl":"10.1186/s13287-025-04446-8","url":null,"abstract":"<p><strong>Background: </strong>Acute graft-versus-host disease (aGVHD) is a life-threatening complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT), particularly if treatment is refractory. Mesenchymal stromal cells (MSCs) have demonstrated promising therapeutic effects in aGVHD, due to their well-described immunomodulatory properties. Based on the importance of maternal-fetal interface immune tolerance, the umbilical cord may provide a superior tissue source of MSC. This study aimed to investigate the safety and efficacy of human umbilical cord derived MSCs (hUC-MSCs) delivered as salvage therapy for steroid-refractory (SR)-aGVHD.</p><p><strong>Methods: </strong>This phase Ib/IIa, multicenter, open-label clinical trial of a third-party, off-the-shelf preparation of hUC-MSCs enrolled grades II to IV SR-aGVHD patients. This trial consist of 2 parts: a phase Ib dose escalation part using a standard 3 + 3 design, which planed twice weekly i.v. infusions of hUC-MSCs, at 0.5 × 10⁶ per kg, 1.0 × 10⁶ per kg and 2.0 × 10⁶ per kg for 3 weeks, to determine the maximum tolerated dose and recommended phase 2 dose (RP2D). Phase IIa of this work is an expansion cohort study of hUC-MSCs at RP2D. The primary endpoint of the study was safety and RP2D. The key secondary endpoints were efficacy of the overall response rate (ORR) at Day 28.</p><p><strong>Results: </strong>The study enrolled 25 patients with SR-aGVHD who received different doses of hUC-MSCs treatment. Safety analysis showed that no dose-limiting toxicity was observed in all dose groups. An ORR of 80.0% was achieved by day 28, with a complete response rate of 40.0% and a partial response rate of 40.0%. The incidence, severity, and type of adverse events (AEs) were similar across different dose groups, showing no obvious correlation with dose. The RP2D was determined to be 1.0 × 10⁶ per kg. The 1-year overall survival rate was 74.3%. The 1-year incidence of non-relapse mortality and relapse of the underlying malignancy after SCT was 17.0% and 8.4%, respectively. Biomarker analysis showed that in responding patients, the proportion of CD8 + central memory T cells and CXCR-10 levels significantly increased at 24 h after hUC-MSCs infusion.</p><p><strong>Conclusions: </strong>The remarkable efficacy and favorable safety profile of hUC-MSCs offer a promising salvage therapy for patients with severe SR-aGVHD.</p><p><strong>Trial registration: </strong>CTR20221330. Registered 06 June 2022, http://www.chinadrugtrials.org.cn/clinicaltrials.searchlistdetail.dhtml .</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"345"},"PeriodicalIF":7.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12219234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144544943","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":"Human platelet lysate standardization across three independent European blood establishments.","authors":"Willem Delabie, Gabriele Boretti, Stephanie A Groot, Davina Ardanary, Olafur Sigurjónsson, Thomas R L Klei, Philippe Vandekerckhove, Hendrik B Feys","doi":"10.1186/s13287-025-04445-9","DOIUrl":"10.1186/s13287-025-04445-9","url":null,"abstract":"<p><p>Human platelet lysate (hPL) is a clinically safe alternative to fetal bovine serum (FBS). However, variability in blood donation practices, platelet concentrate preparation methods, storage and hPL manufacturing complicates standardization across jurisdictions. This study aimed to establish a first multinational hPL manufacturing standardization across three European blood centers to test feasibility and variability. A single batch of hPL production sets was distributed to the participating centers. There, hPL was produced following a single standard operating protocol but starting from each center's unique platelet concentrates. Each center prepared four 'national' hPL batches and four 'international' batches. Researchers conducted blinded quality and variation analyses to ensure unbiased results. All hPL batches exhibited comparable total protein levels, pH, ionic strength, and lactate content. Analysis of twelve growth factors showed minor variations across batches. Endothelial cell outgrowth and wound closure were slower in hPL than FBS but remained consistent across batches. Mesenchymal stem cell (MSC) doubling was significantly faster in hPL than in FBS, with MSC phenotype consistency confirmed via flow cytometry. Differentiation into adipogenic and osteogenic tissue was successful in all hPL samples. The inter-institutional variation across all national batches was higher for all critical outcome parameters compared to the variation in the four international batches. These findings confirm the feasibility of manufacturing standardized hPL across borders and show lower variability when doing so. This supports further efforts to stabilize hPL supply and advance cytotherapy standardization in Europe.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"329"},"PeriodicalIF":7.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12210671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144544933","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":"MiR-145 encapsulated small extracellular vesicles inhibit colorectal cancer progression by downregulating fascin actin-bundling protein 1 expression.","authors":"Yanxia Chen, Meijuan He, Lei Cui, Jianguo Zhang, Hanpeng Huang, Zhimin Tao","doi":"10.1186/s13287-025-04456-6","DOIUrl":"10.1186/s13287-025-04456-6","url":null,"abstract":"<p><strong>Background: </strong>Drug degradation poses a significant challenge in the pursuit of effective gene therapies for cancers.</p><p><strong>Methods: </strong>Here we have developed a bioactive nanosized composite that utilizes human umbilical cord mesenchymal stem cells (hucMSCs) derived small extracellular vesicles (sEVs), to carry tumor suppressor miR-145 alongside erbium-doped rare earth nanoparticles (ErNPs). This approach not only enhances in vivo delivery but also facilitates real-time fluorescence tracking of nucleic acid drugs in the near infrared (NIR) II window. With this technique, we are able to realize and visualize the effective inhibition of colorectal cancer (CRC) progression in a xenografted murine model.</p><p><strong>Results: </strong>Our results revealed that the efficient loading of miR-145 into sEVs could be achieved through a dynamic combination of sonication and electroporation. The resulting miR-145-encapsulated sEVs (i.e., miRNA@sEVs) exhibited a profound ability to hinder tumor growth by effectively downregulating the expression of fascin actin-bundling protein 1 (FSCN1), both in vitro and in vivo. Additionally, the circulation half-time of miRNA@sEVs was measured to be ~ 4 h and the fluorescence at the tumor sites reached a peak intensity at ~ 8 h after intravenous injection of sEVs particles. Finally, the fluorescent signals of miRNA@sEVs were predominantly localized in the mouse liver and spleen, with substantial accumulation in tumors.</p><p><strong>Conclusions: </strong>Our results illuminated the excellent biosafety of miRNA@sEVs and their high accumulation in tumors, leading to efficient suppression of tumor progression. This research heralds a promising advancement in gene therapy, paving the way for more effective and safer treatment options.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"343"},"PeriodicalIF":7.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12220125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144544938","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":"Renin-angiotensin system as an emerging target to modulate adult neurogenesis in health and disease.","authors":"Jannette Rodríguez-Pallares, Lucia A Garcia-Crivaro, Juan A Parga, Jose Luis Labandeira-Garcia","doi":"10.1186/s13287-025-04430-2","DOIUrl":"10.1186/s13287-025-04430-2","url":null,"abstract":"<p><p>Adult neurogenesis is a complex multiphase process involving the formation and integration of new neurons into existing brain circuits. Although it was first described over 50 years ago and numerous factors involved in regulating neurogenic niches have been extensively studied, the underlying molecular mechanisms and interactions involved in controlling adult neurogenesis are still not fully understood. The renin-angiotensin system (RAS) is a well-known hormonal system that controls water and electrolyte balance and blood pressure. In addition to the circulating RAS, a local brain RAS has been described, with a key role in brain homeostasis. A wealth of evidence has emerged showing the involvement of RAS in neurodegeneration and neuroinflammation as well as in proliferation, differentiation, survival, and regeneration processes. Moreover, RAS has a role in cognitive function, behavioral responses, and dementia, which are closely related to neurogenic areas. This review summarizes the current evidence on the role of RAS in regulating adult neurogenic niches. We critically discuss pre-clinical and clinical studies investigating the role of RAS as a potential therapeutic target to modulate neurogenesis in pathological conditions.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"332"},"PeriodicalIF":7.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12210598/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144544942","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":"The circ_0054633/miR-590-3p/RUNX2 positive feedback loop promotes the osteogenic differentiation of BMSCs.","authors":"Lingxiao Wang, Yang Liu, Zhanqiu Diao, Yishu Huang, Haoqing Yang, Yue Zhang, Bowen Zhou, Zhenhua Gao, Zhaochen Shan, Jun Li, Zhipeng Fan","doi":"10.1186/s13287-025-04450-y","DOIUrl":"10.1186/s13287-025-04450-y","url":null,"abstract":"<p><strong>Background: </strong>Mandibular bone marrow stem cells (BMSCs) from patients with type 2 diabetes mellitus (T2DM) have poor osteogenic differentiation capacity. Elucidating the molecular mechanisms by which circular RNAs (circRNAs) play specific roles in T2DM will reveal new diagnostic biomarkers and therapeutic targets.</p><p><strong>Methods: </strong>BMSCs with different circ_0054633 expression levels were generated. Furthermore, alkaline phosphatase (ALP) activity, alizarin red staining (ARS), and transplantation of HA/tricalcium phosphate into BMSCs were performed to detect the osteogenic effects of different levels of circ_0054633 expression in BMSCs in vivo and in vitro.</p><p><strong>Results: </strong>In this study, we identified 80 differentially expressed circRNAs in jawbone-derived BMSCs from patients with T2DM. Notably, significant downregulation of circ_0054633 promoted the osteogenic differentiation of these cells in vitro and in vivo. Mechanistically, circ_0054633 acts as a miRNA sponge; specifically, it actively regulates the expression of RUNX2 by sponging miR-590-3p and thus promoting the osteogenic differentiation of the BMSCs. In addition, we found that circ_0054633 was a direct transcriptional target of RUNX2. RUNX2 overexpression activated the circ_0054633 promoter and promoted the generation of nuclear circ_0054633, whereas RUNX2 knockdown abrogated the osteogenic role of circ_0054633 and formed a circ_005463/miR-590-3p/RUNX2 positive feedback loop.</p><p><strong>Conclusions: </strong>Our results suggest that the circ_0054633/miR-590-3p/RUNX2 positive feedback loop promotes the osteogenic differentiation of BMSCs and is expected to be a potential biomarker and therapeutic target for bone regeneration in T2DM.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"325"},"PeriodicalIF":7.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12210457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144544946","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":"Production of bioactive cytokines using plant expression system for cardiovascular cell differentiation from human pluripotent stem cells.","authors":"Kozue Murata, Kanae Takamura, Risa Watanabe, Akitomo Nagashima, Miho Miyauchi, Yoshiteru Miyauchi, Hidetoshi Masumoto","doi":"10.1186/s13287-025-04424-0","DOIUrl":"10.1186/s13287-025-04424-0","url":null,"abstract":"<p><p>Bioactive cytokines such as vascular endothelial growth factor (VEGF) and Activin A are critical for the differentiation of stem cells into vascular endothelial cells and cardiomyocytes. However, production of the cytokines using conventional Escherichia coli or mammalian cell expression systems carries risks of immunogenicity and viral contamination. In this study, we developed a VEGF and Activin A plant expression system and demonstrated that plant-expressed VEGF and Activin A are as active as their commercial counterparts. We also showed that plant-expressed VEGF and Activin A are as efficient as human recombinant counterparts in inducing endothelial cells and cardiomyocytes from human pluripotent stem cells. These results suggest that plant-expressed VEGF and Activin A are promising alternatives for the safe and efficient production of cardiac cells, specifically cardiomyocytes and endothelial cells, for stem cell-based regenerative medicine.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"303"},"PeriodicalIF":7.1,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188682/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485701","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":"LINC01013 reverses bisphosphonate-impaired osteogenic differentiation of JBMMSCs by regulating intracellular translocation of ILF3.","authors":"Jiaxin Song, Wanqing Wang, Xuanhe Feng, Haoqing Yang, Zhaochen Shan, Zhipeng Fan","doi":"10.1186/s13287-025-04467-3","DOIUrl":"10.1186/s13287-025-04467-3","url":null,"abstract":"<p><strong>Background: </strong>Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a serious complication associated with bisphosphonate (BP) therapy. Enhancement of the osteogenic differentiation of human jaw bone marrow mesenchymal stem cells (JBMMSCs) is a key issue in the treatment of BRONJ. In this study, we investigated the role and mechanism of LINC01013 in regulating osteogenic differentiation of JBMMSCs.</p><p><strong>Methods: </strong>Osteogenic differentiation of JBMMSCs was assessed in vitro using alkaline phosphatase (ALP), alizarin red staining (ARS), and western blotting. JBMMSCs transplanted into the backs of nude mice were used to detect JBMMSCs osteogenesis in vivo. Molecular mechanisms involved in JBMMSCs osteogenesis were evaluated using real-time fluorescence quantitative polymerase chain reaction, western blotting, fluorescence in situ hybridization, RNA pull-down, and RNA-seq.</p><p><strong>Results: </strong>Homeobox C8 (HOXC8) knockdown enhanced ALP activity, ARS, and expression of bone sialoprotein and osteocalcin in JBMMSCs under normal and BP stimulation conditions. HOXC8 negatively regulated LINC01013 expression. LINC01013 enhanced JBMMSCs osteogenic differentiation impaired by BP stimulation. Furthermore, LINC01013 regulated the expression of inflammation-related genes in JBMMSCs under BP conditions. LINC01013 formed a complex with ILF3. Two isoforms of ILF3 (NF90 and NF110) promoted the osteogenic differentiation of JBMMSCs under normal and BP conditions, depending on their nuclear localization. Additionally, NF90, which is located in the nucleus, inhibited the expression of NLR family pyrin domain containing 3 (NLRP3).</p><p><strong>Conclusions: </strong>In summary, HOXC8 negatively regulates LINC01013 to inhibit osteogenic differentiation of JBMMSCs under BP conditions. We also further clarified that LINC01013 binding to ILF3 affects ILF3 nuclear localization to regulate JBMMSCs osteogenic differentiation and regulates NLRP3/Caspase-1 pathway to affect JBMMSCs function under BP stimulation.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"319"},"PeriodicalIF":7.1,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12186329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476741","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":"Enhancing retention and quality of tissue stromal vascular fraction graft with globo H ceramide.","authors":"Jing-Yan Cheng, Hui-Yun Cheng, Jung-Tung Hung, Gonzalo Mallarino Restrepo, Shih-Pin Chiou, Ling-Yi Shih, Alice L Yu, Huang-Kai Kao, John Yu, Fu-Chan Wei","doi":"10.1186/s13287-025-04395-2","DOIUrl":"10.1186/s13287-025-04395-2","url":null,"abstract":"<p><strong>Background: </strong>Fat grafting has been extensively used in plastic surgery practice, yet unstable retention in the recipient site remains a significant clinical challenge. The limited tolerance of injected adipose tissue to ischemia has prompted strategies aiming at timely enhancing the vascularity of the grafted fat. Various modified fat graft preparations have been used, and the mechanically processed tissue stromal vascular fraction (tSVF) derived from fat tissue has garnered considerable interest for enhancing rate of fat graft retention. Further enhancement of the graft retention and quality through supplements to tSVF is worthy of investigation.</p><p><strong>Methods: </strong>The arteriovenous (AV) shunt in rats has been used to evaluate tSVF in vivo. We employed this animal model to investigate the regenerative potential of glycolipid Globo H Ceramide (GHCer) added to tSVF isolated from male Lewis rats. Sixty-two rats divided into four groups were studied. Study parameters included gene expression of vascular endothelial growth factor A (VEGFA) and fatty acid binding protein 4 (FABP4), percentages of the CD45^-CD31⁺ endothelial cell, fat tissue retention and fibrotic changes. In vitro studies on adipose-derived mesenchymal stromal cells (AD-MSCs) included angiogenesis by tube formation assay and adipogenesis.</p><p><strong>Results: </strong>The addition of GHCer resulted in superior retention of the tSVF grafts at one-, two-, and eight-week post-grafting (p < 0.05). Elevated expression VEGFA was observed from one week (p < 0.05), followed by FABP4 at two weeks post-grafting in the tSVF + GHCer grafts (p < 0.01). After eight weeks, the numbers of CD45^-CD31⁺ endothelial cells and adipocytes were significantly increased in the tSVF + GHCer grafts (p < 0.01), while collagen deposition was reduced (p < 0.05). Given that GHCer potentially exerted its effects on tSVF through AD-MSCs within, we performed in vitro studies and demonstrated that GHCer promoted AD-MSC differentiation into neovessels (p < 0.05) and adipocytes (p < 0.001).</p><p><strong>Conclusions: </strong>Supplementing GHCer to tSVF effectively reduced fat reabsorption and fibrotic changes of the grafts, while enhancing angiogenesis and adipogenesis, potentially through facilitating AD-MSC differentiation within tSVF. These findings support the potential clinical application of GHCer to enhance the stability and long-term outcomes of fat grafting procedures.</p><p><strong>Trial registration: </strong>Not applicable.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"317"},"PeriodicalIF":7.1,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12186370/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476740","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}