Stem Cell Research & Therapy最新文献

{"title":"Enhance the therapeutic efficacy of human umbilical cord-derived mesenchymal stem cells in prevention of acute graft-versus-host disease through CRISPLD2 modulation.","authors":"Qing Xu, Rui Wang, Ke Sui, Yuxi Xu, Ya Zhou, Yuxuan He, Ziyi Hu, Qi Wang, Xiaodong Xie, Xiaoqi Wang, Shijie Yang, Lingyu Zeng, Jiang F Zhong, Zheng Wang, Qingxiao Song, Xi Zhang","doi":"10.1186/s13287-025-04321-6","DOIUrl":"https://doi.org/10.1186/s13287-025-04321-6","url":null,"abstract":"<p><strong>Background: </strong>Acute graft-versus-host disease (aGVHD) remains a major life-threatening complication of allogeneic haematopoietic cell transplantation (allo-HSCT), often limiting the therapeutic efficacy of allo-HSCT. Recent studies have suggested that mesenchymal stem cells (MSCs) may be beneficial for the treatment of aGVHD. However, the therapeutic potential of MSCs is often negatively impacted by their heterogeneity.</p><p><strong>Methods: </strong>To investigate MSCs heterogeneity, we conducted single-cell transcriptomic analysis of human umbilical cord-derived MSCs (HUC-MSCs) and identified key feature genes that distinguish MSCs subpopulations. The function of the newly discovered biomarker CRISPLD2 was also explored. We engineered human umbilical cord-derived MSCs (HUC-MSCs) to overexpress the CRISPLD2 gene using lentiviral vectors. The downstream regulatory effects of CRISPLD2 overexpression were assessed through bulk RNA sequencing. Additionally, we evaluated its impact on cellular senescence using Western blotting and β-galactosidase (SA-β-gal) staining. The immunoregulatory capability of HUC-MSCs was tested through coculture experiments with T cells and liver organoids in vitro. Mitochondrial function was analysed via flow cytometry and electron microscopy. The in vivo therapeutic effects of HUC-MSCs on aGVHD were evaluated using an aGVHD murine model. The graft-versus-leukaemia (GVL) effect was measured via the inoculation of luciferase-positive A20 cells, and tumour growth was monitored via bioluminescence imaging.</p><p><strong>Results: </strong>Our findings indicated that the CRISPLD2 gene is heterogeneously expressed in HUC-MSCs subsets characterized by stemness and immunosuppressive properties. Transcriptomic analysis revealed that CRISPLD2 overexpression suppressed calcium ion binding and G protein-coupled receptor signalling. In vitro studies demonstrated a marked increase in IL-10 secretion, which enhanced T-cell suppression in CRISPLD2-modified HUC-MSCs. The in vivo results demonstrated that transfusion of CRISPLD2-overexpressing HUC-MSCs ameliorated aGVHD while maintaining GVL activity. Mechanistically, CRISPLD2 overexpression overcomes the mitochondrial damage mediated by extracellular ATP and LPS in HUC-MSCs by inhibiting P2Y11 receptor signalling, thereby preserving their stemness and IL-10-mediated immunosuppressive functions.</p><p><strong>Conclusions: </strong>Our study revealed that CRISPLD2 is a novel marker for identifying HUC-MSCs subpopulation with enhanced immunosuppressive functions. CRISPLD2 overexpression enhances the immunosuppressive function of HUC-MSCs by inhibiting P2Y11 receptor signalling. Targeting CRISPLD2 is a promising strategy to improve the therapeutic efficacy of HUC-MSCs in aGVHD while maintaining GVL activity.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"222"},"PeriodicalIF":7.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12044869/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144064505","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":"DSUP modified mesenchymal stem cells exert significant radiation protective effect by enhancing the hematopoietic niche.","authors":"Fu-Dong Chen, Biao Zhang, Li-Li Wang, Ya-Li Jia, Quan Zeng, Tao Fan, Hai-Yang Wang, Ming-Fang Xiong, Ying-Xue Lin, Jun-Nian Zhou, Wen Yue, Li Chen, Jia-Fei Xi","doi":"10.1186/s13287-025-04300-x","DOIUrl":"https://doi.org/10.1186/s13287-025-04300-x","url":null,"abstract":"<p><strong>Background: </strong>Radiation induced hematopoietic failure was the primary cause of death after exposure to a moderate or high dose of whole body irradiation, causing increased challenge for nuclear or radiological treatment, so it is an urgent need to develop radioprotectors for attenuating hematopoietic damage caused by acute radiation syndrome (ARS). Given the excellent therapeutic effects and special benefits of mesenchymal stem cells (MSCs) in radiation damaged hematopoietic stem/progenitor cells (HSPCs) recovery and hematopoietic niche reconstruction, enhancing the hematopoietic niche with the radiotolerance MSCs can be an alternative solution to prevent and attenuate hematopoietic radiation damage, which needs to be studied.</p><p><strong>Methods: </strong>Here, we constructed MSCs modified with Damage Suppressor Protein (DSUP), a radiotolerance gene identified from tardigrade Ramazzotius varieornatus, and verify its radiation protection effect in HSPCs-MSCs co-culture model in vitro and radiation damaged mice model in vivo.</p><p><strong>Results: </strong>Our results showed that DSUP protein had no significant toxic side effects on the basic stemness properties and differentiation potential of MSCs, and significantly enhanced the radiation tolerance and DNA protection ability of MSCs. Compared with the control (CON) group MSCs, the DSUP modified MSCs after radiation damage suffered less DNA damage, preserved most of proliferation activity and migration ability. In the HSPCs-MSCs co-culture model, DSUP modified MSCs have significant protective effect on HSPCs by providing a functional hematopoietic niche after radiation damage. The DSUP group irradiated HSPCs exhibited more rapid recovery, the higher HSPCs ratio and better hematopoietic differentiation potential. In animal studies, pre infusion of DSUP modified MSCs reduce irradiated mice mortality rate, reduce hematopoietic failure incidence, and provide a protective effect against radiation injury by protecting hematopoietic microenvironment and promoting HSCs recovery. DSUP modified MSCs can be used as a radioprotector and existed significant radiation protection effect for ARS at doses below 7 Gy total-body irradiation (TBI) of X-ray in both immunodeficient and immunocompetent mice models.</p><p><strong>Conclusions: </strong>DSUP modified MSCs may serve as a new radioprotector for ARS. DSUP modified MSCs could attenuate radiation damage of HSPCs and promote HSPCs rapid recovery as well as hematopoietic reconstruction by providing a more functional niche after radiation, thereby reducing the occurrence of hematopoietic failure and improving survival rate.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"216"},"PeriodicalIF":7.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12045013/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982961","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":"Bone marrow mesenchymal stem cells alleviate liver fibrosis after rat liver transplantation through JAK1/STAT5 pathway.","authors":"Zhuyuan Si, Shengqiao Zhao, Zhixin Zhang, Tianran Chen, Ruofan Wang, Chong Dong, Kai Wang, Chao Sun, Zhuolun Song, Zhongyang Shen, Wei Gao","doi":"10.1186/s13287-025-04353-y","DOIUrl":"https://doi.org/10.1186/s13287-025-04353-y","url":null,"abstract":"<p><strong>Objective: </strong>The effectiveness of bone marrow mesenchymal stem cells (BMSCs) in post-transplantation liver fibrosis has not been studied. The aim of this study was to investigate the effect of BMSCs on liver fibrosis and their role in the Janus-activated kinase (JAK) 1/ signal transducer and activator of transcription (STAT) 5 pathway after liver transplantation (LT).</p><p><strong>Methods: </strong>A rat model of post-LT liver fibrosis induced by cold ischemia injury was successfully established. BMSCs were injected into the rats through the portal vein. Hepatic stellate cell (HSC)-T6 were co-cultured with BMSCs in vitro after hypoxia-reoxygenation. JAK1 inhibitor Abrocitinib and JAK1 agonist RO8191 were used to study the JAK1/STAT5 signaling pathway.</p><p><strong>Results: </strong>BMSCs significantly alleviated liver fibrosis caused by cold ischemia-reperfusion injury after rat LT in vivo. After BMSCs transplantation, the levels of JAK1 and p-STAT5 in rat liver were significantly reduced. After using Abrocitinib, the stage of liver fibrosis and the levels of collagen type I alpha 1 chain (COL1A1) and actin alpha 2 (ACTA2) decreased. After using RO8191, the stage of liver fibrosis and the levels of COL1A1 and ACTA2 increased. BMSCs significantly reduced the activation of HSC-T6 after hypoxia-reoxygenation in vitro. After co-culturing with BMSCs after HSC-T6 hypoxia-reoxygenation, the levels of JAK1 and p-STAT5 were significantly reduced. After the addition of Abrocitinib, the levels of COL1A1 and ACTA2 decreased in HSC-T6; in contrast, after adding RO8191, the levels of COL1A1 and ACTA2 increased in HSC-T6 after hypoxia-reoxygenation. After using anti-IL7 antibody or anti-IL7Rα in vivo and in vitro, the stage of liver fibrosis and the levels of COL1A1 and ACTA2 decreased as well as the phosphorylation level of STAT5.</p><p><strong>Conclusions: </strong>BMSCs alleviate hepatic cell damage, reduce hepatic cell-derived IL7, downregulate IL7R/JAK1/STAT5 in HSCs, thereby reducing HSCs' activation and ultimately alleviating liver fibrosis after liver transplantation.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"217"},"PeriodicalIF":7.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12044927/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144052627","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":"Exploring extracellular vesicles as novel therapeutic agents for intervertebral disc degeneration: delivery, applications, and mechanisms.","authors":"Yuxin Jin, Ouqiang Wu, Zhihua Chen, Linjie Chen, Kai Zhang, Qizhu Chen, Haijun Tian, Xinzhou Wang, Morgan Jones, Kenny Yat Hong Kwan, Yan Michael Li, Pooyan Makvandi, Xiangyang Wang, Xiang Hai, Jun Zhang, Aimin Wu","doi":"10.1186/s13287-025-04299-1","DOIUrl":"https://doi.org/10.1186/s13287-025-04299-1","url":null,"abstract":"<p><p>Intervertebral disc degeneration is a multifactorial degenerative disease that poses a significant threat to the health of the elderly population. Current treatments primarily focus on physical therapy, medication, and surgery to alleviate symptoms associated with disc compression but do not address the progression of degeneration. Therefore, this review aimed to explore the potential of extracellular vesicle therapy as a novel preventive strategy to delay degeneration and enhance tissue repair in intervertebral discs. We cover the pathogenic mechanisms underlying intervertebral disc degeneration, including inflammation, apoptosis, pyroptosis, ferroptosis, autophagy dysregulation, and the roles of non-coding RNAs. Subsequently, we discussed the therapeutic potential of extracellular vesicles and their molecular components, such as proteins, RNAs, and lipids, in modulating these pathways to counter intervertebral disc degeneration. We provides a comprehensive review of the significant role of extracellular vesicle cargo in mediating repair mechanisms. It discusses the functional enhancement advantages exhibited by extracellular vesicles under current bioengineering modifications and drug loading. The challenges and future prospects of utilizing extracellular vesicle therapy to treat this degenerative condition are also summarized.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"221"},"PeriodicalIF":7.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12044939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144048833","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":"Harnessing the angiogenic potential of adipose-derived stromal vascular fraction cells with perfusion cell seeding.","authors":"Gregory Reid, Giulia Cerino, Ludovic Melly, Deborah Fusco, Chunyan Zhang, Oliver Reuthebuch, Giulia Milan, Anna Marsano","doi":"10.1186/s13287-025-04286-6","DOIUrl":"https://doi.org/10.1186/s13287-025-04286-6","url":null,"abstract":"<p><strong>Background: </strong>The rapid formation and long-term maintenance of functional vascular networks are crucial for the success of regenerative therapies. The stromal vascular fraction (SVF) from human adipose tissue is a readily available, heterogeneous cell source containing myeloid lineage cells, mesenchymal stromal cells, endothelial cells and their precursors, and pericytes, which are important for vascular support. Previous studies showed that seeding SVF cells under perfusion and pre-culturing them on three-dimensional (3D) collagen sponges enhances the vascular cell component in vitro while accelerating vascularization and improving human cell engraftment in vivo compared to static pre-culture. However, generating a perfusion-cultured SVF patch over a 5-day period is both costly and challenging for clinical translation. To overcome these limitations, this study explores a no-pre-culture strategy by comparing perfusion-based seeding with static cell loading on 3D sponges. The hypothesis is that perfusion-based seeding enhances in vivo cell engraftment and angiogenic potential by loading different SVF cell subpopulations onto 3D scaffolds during the seeding process.</p><p><strong>Methods: </strong>SVF-cells are seeded onto collagen scaffold using two approaches: a closed system perfusion bioreactor for 18 h or static loading onto the sponge surface. The in vitro cell distribution and baseline cytokine profiles were evaluated. Subsequently, human cell engraftment and differentiation were assessed in vivo using a nude rat subcutaneous implantation model. Analyses included the survival of transplanted human cells, the functionality and maturation of newly formed blood vessels within the SVF-patch.</p><p><strong>Results: </strong>Perfusion seeding significantly reduced the number of myeloid cells and achieved uniform spatial distribution across the construct. Vascular endothelial growth factor release was significantly increased following perfusion culture, whereas pro-inflammatory cytokines such as tumor necrosis factor-α and interleukin-1β were decreased. In the short term, perfusion culture enhanced uniform vascularization and SVF cell engraftment in vivo. However, the long-term differences between the perfusion-seeded and static-seeded groups diminished.</p><p><strong>Conclusion: </strong>Eliminating the need for prolonged pre-culture offers a feasible and cost-effective strategy for advancing regenerative cell-based therapies by reducing pre-culture times while preserving therapeutic efficacy. Perfusion-based seeding offers significant short-term benefits, including enhanced vascularization and cell engraftment, though long-term differences compared to static seeding are minimal. Further investigation is needed to evaluate its potential in a diseased ischemic heart model.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"220"},"PeriodicalIF":7.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12044990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986653","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":"Phase separation participates in the genetic regulation mechanism of hematopoietic stem cells: potential therapeutic methods.","authors":"XinYu Tang, Yan Wang, RuiRong Xu","doi":"10.1186/s13287-025-04350-1","DOIUrl":"https://doi.org/10.1186/s13287-025-04350-1","url":null,"abstract":"<p><p>Hematopoietic stem cells (HSCs) are the primitive cells that give rise to common precursors for all blood cell lineages. Abnormalities in their number and/or function are important factors leading to the decline of immune function and the occurrence of various systemic diseases. Phase separation refers to a physicochemical mechanism in which intracellular liquid-liquid phase separation (LLPS) forms membrane-less organelles. It participates in various physiological activities and is related to the occurrence of diseases. Studies have shown that the functional activity of HSCs is regulated by complex mechanisms, and phase separation is closely related to these complex mechanisms such as genetic regulation, epigenetic regulation, microenvironment regulation, gene expression, autophagy degradation, and cell proliferation. With the deepening of research, the importance of phase separation in the pathogenesis and treatment of diseases such as leukemia and tumors has gradually emerged, but the deep mechanism of its regulation of HSCs genetic regulation still lacks exploration, and the direction of clinical targeted therapy is not yet clear. Here, we will summarize and elaborate the genetic regulation mechanism of HSCs, discuss the relationship between phase separation and the functional regulation of HSCs, and analyze the possibility of phase separation participating in the genetic regulation of HSCs to treat diseases, in order to provide help for the clinical implementation of targeted therapy for HSCs regulation.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"214"},"PeriodicalIF":7.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12044980/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144038372","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":"Puerarin relives inflammation, bone destruction and facilitates osteogenic differentiation in periodontitis by enhancing mitochondrial autophagy via activating mitochondrial Mitofusin 2.","authors":"Yulan Xiang, Zelu Li, Xin He, Xiaoyang Chu, Chunyan Gao, Jiahao Guo, Yingyi Luan, Kai Yang, Dongliang Zhang","doi":"10.1186/s13287-025-04355-w","DOIUrl":"https://doi.org/10.1186/s13287-025-04355-w","url":null,"abstract":"<p><strong>Purpose: </strong>Puerarin (Pue) has recently been reported to have therapeutic effects on periodontitis (PD). However, there is insufficient evidence, and the mechanism involved has not yet been revealed. This work delved to explore the exact therapeutic effects and molecular mechanism of Pue in treating PD.</p><p><strong>Methods: </strong>PD mouse (C57BL/6 N mouse) model constructed by Porphyromonas gingivalis-lipopolysaccharide (Pg-LPS) induction was treated with Pue. Therapeutic efficacy of Pue for PD was examined by a series of experiments. PD cell model was induced by treating human periodontal ligament cells with Pg-LPS. Therapeutic effects of Pue on PD cell model, along with the potential molecular mechanism, were explored by logical experiments. Rescue experiments based on in vitro and in vivo studies were implemented to validate the molecular mechanism of Pue in treating PD.</p><p><strong>Results: </strong>In PD mice, Pue treatment relieved inflammation and bone destruction, facilitated osteogenic differentiation and autophagy in periapical tissues. In PD cell model, Pue treatment facilitated osteogenic differentiation and mitochondrial autophagy; suppressed inflammation and mitochondrial reactive oxygen species; maintained mitochondrial membrane potential and mitochondrial kinetic homeostasis; and activated mitochondrial Mitofusin 2 (Mfn2). However, these influences of Pue on PD cell model were eliminated by CsA (mitochondrial autophagy inhibitor). The enhanced mitochondrial autophagy induced by Pue was reversed by Mfn2 silencing. Through in vivo data, Mfn2 knockdown counteracted the therapeutic effects of Pue on PD mice.</p><p><strong>Conclusion: </strong>Pue exerted therapeutic effects on PD, possibly by enhancing mitochondrial autophagy via activating mitochondrial Mfn2. This might be a cure for PD.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"218"},"PeriodicalIF":7.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12044717/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144035556","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":"Targeting prominin-2/BACH1/GLS pathway to inhibit oxidative stress-induced ferroptosis of bone mesenchymal stem cells.","authors":"Yuzhu Xu, Lele Zhang, Xuanfei Xu, Yuao Tao, Pengfei Xue, Yuntao Wang, Renjie Chai, Xiaotao Wu","doi":"10.1186/s13287-025-04326-1","DOIUrl":"https://doi.org/10.1186/s13287-025-04326-1","url":null,"abstract":"<p><p>Suppressing bone mesenchymal stem cell (BMSC) ferroptosis is expected to optimize BMSCs-based therapy for intervertebral disc degeneration (IVDD). Our previous study revealed that Prominin-2 could protect against ferroptosis by decreasing cellular Fe²⁺ content and inhibiting transcription regulator protein BACH1 (BACH1) expression. In this study we probed the molecular mechanisms underlying the Prominin-2/BACH1 pathway in BMSC ferroptosis. Using an array of in vitro and in vivo experiments we found that heat shock factor protein 1 (HSF1) activates PROM2 (encoding protein Prominin-2) transcription and elevated Prominin-2 expression. Furthermore, we showed that Prominin-2 attenuates ferroptosis induced by tert-butyl hydroperoxide (TBHP) through promoting BACH1 ubiquitination and degradation. Inhibition of BACH1 expression reversed TBHP-stimulated down expression of glutaminase kidney isoform, mitochondrial (GLS), which plays a crucial role in protecting BMSCs against ferroptosis. Targeting the Prominin-2/BACH1 axis has also been shown to improve BMSC survival post-transplantation and mitigate IVDD progression by inhibiting ferroptosis. Our results support a new mechanistic insight into the regulation of the Prominin-2/BACH1/GLS pathway in BMSC ferroptosis. These finding could lead to potential therapeutic targets to improve the survival of engrafted BMSCs under oxidative stress circumstances.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"213"},"PeriodicalIF":7.1,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12042394/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144048835","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":"Poly-ε-caprolactone/chitosan/whitlockite electrospun bionic membrane conjugated with an E7 peptide for bone regeneration.","authors":"Guangzi Chen, Tao Xu, Ran Gao, Wenbin Liu, Weigang Li, Delu Zeng, Jian Li, Xuan Fang, Gaohong Sheng, Hongqi Zhao, Chaoxu Liu","doi":"10.1186/s13287-025-04307-4","DOIUrl":"https://doi.org/10.1186/s13287-025-04307-4","url":null,"abstract":"<p><strong>Background: </strong>Periosteum plays an important role in bone defect repair due to its rich vascular network and cells. However, natural periosteum is difficult to meet clinical requirements due to its low availability. Therefore, it is necessary to develop a tissue engineering strategy of biomimetic periosteum for bone defect repair.</p><p><strong>Methods: </strong>Poly-ε-caprolactone/chitosan/Whitlockite electrospun bionic membrane (PCL/CS/WH) was prepared using electrospinning technology, then it was conjugated with an E7 peptide as PCL/CS/WH/E7 bionic membrane. The physical properties of the membranes were evaluated by TEM, FTIR and tensile strength testing. In vitro, LIVE/DEAD staining and Cell Counting Kit-8 assay of bone marrow mesenchymal stem cells (BMSCs) and Endothelial progenitor cells (EPCs) are used to assess the biocompatibility of bionic membranes. Matrigel was applied to evaluate the ability of the different composite nanofibers samples to promote angiogenesis. Mineralized nodule and collagen formation in the BMSCs was detected by alizarin red staining and sirius red staining respectively. The expression of osteogenesis related genes and angiogenesis associated genes were detected using quantitative real-time polymerase chain reaction (qRT-PCR). In vivo, the ability of PCL/CS/WH/E7 membrane to promote bone regeneration and angiogenesis was assessed by Micro-CT and associated staining.</p><p><strong>Result: </strong>The addition of chitosan (CS) and E7 peptide (E7) enhanced the hydrophilicity and cytocompatibility of pure PCL membranes. Additionally, CS, E7 and Mg²⁺ released from Whitlockite (WH) had a synergistic effect to promote angiogenesis and osteogenic differentiation. Three weeks after implantation, the membrane successfully bridged the bone defect and significantly promoted the formation of new bone and blood vessels.</p><p><strong>Conclusion: </strong>The PCL/CS/WH/E7 membrane to achieve efficient repair of bone tissue and enriches clinical solutions for the treatment of critical bone defects.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"212"},"PeriodicalIF":7.1,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12039202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982963","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":"Treatment of osteoarthritic knee with high tibial osteotomy and allogeneic human umbilical cord blood-derived mesenchymal stem cells combined with hyaluronate hydrogel composite.","authors":"Bo Seung Bae, Jae Woong Jung, Gyeong Ok Jo, Seon Ae Kim, Eun Jeong Go, Mi-La Cho, Asode Ananthram Shetty, Seok Jung Kim","doi":"10.1186/s13287-025-04356-9","DOIUrl":"https://doi.org/10.1186/s13287-025-04356-9","url":null,"abstract":"<p><strong>Background: </strong>Delaying total knee arthroplasty is crucial for middle-aged patients with severe osteoarthritis. The long-term outcomes of high tibial osteotomy (HTO) remain uncertain. Recently, mesenchymal stem cells (MSCs) have shown promising potential in enhancing cartilage regeneration. Therefore, this study aimed to assess cartilage regeneration following the implantation of allogeneic human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) with HTO.</p><p><strong>Methods: </strong>In this case series, ten patients underwent hUCB-MSC implantation with HTO. The median age was 58.50 (range: 57.00-60.00) years, and the mean body mass index was 27.81 (range: 24.42-32.24) kg/m². Clinical outcomes, including the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), visual analog scale (VAS), Physical Component Score (PCS) and Mental Component Score (MCS) from the 36-Item Short-Form Health Survey (SF-36), were evaluated 6 months, 1 year, and 2 years postoperatively. Cartilage status of the medial femoral condyle (MFC) was assessed during hardware removal surgery, at least 2 years after the initial procedure, and compared with preoperative MFC cartilage status regarding lesion size and International Cartilage Repair Society (ICRS) grade. Radiological assessments included the Kellgren-Lawrence (KL) grading system for medial compartment osteoarthritis and hip-knee-ankle (HKA) angle.</p><p><strong>Results: </strong>Significant improvements were observed in WOMAC scores (preoperative: 57.00 (range: 44.75-63.00), postoperative: 27.50 (range: 22.25-28.75)), VAS scores (preoperative: 66.25 (range: 48.00-74.25), postoperative: 26.25 (range: 14.50-31.13)), SF-36 PCS (preoperative: 27.97 (range: 26.64-31.25), postoperative: 55.31 (range: 51.64-62.50)), and SF-36 MCS (preoperative: 41.04 (range: 29.95-50.96), postoperative: 63.18 (range: 53.83-65.16)) 2 years postoperatively (p = 0.002, 0.002, 0.002, and 0.020, respectively). The MFC chondral lesion demonstrated significant improvement in both lesion size (preoperative: 7.00 cm² (range: 4.38-10.50 cm²), postoperative: 0.16 cm² (range: 0.00-1.75 cm²), p = 0.002) and ICRS grade (preoperative: 4 (range: 4-4), postoperative: 1 (range: 1-2.25), p = 0.002). Additionally, the KL grade significantly decreased from 3 (range: 3-3) preoperatively to 2 (range: 2-2) postoperatively, while the HKA angle was corrected from 7.50° (range: 7.00-10.25°) preoperatively to -1.00° (range: -3.5-0.00°) postoperatively.</p><p><strong>Conclusions: </strong>hUCB-MSC implantation with HTO is an effective treatment for medial compartment osteoarthritis and varus deformities, resulting in significant improvements in cartilage regeneration and overall clinical outcomes.</p><p><strong>Trial registration: </strong>NCT04234412.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"211"},"PeriodicalIF":7.1,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12038988/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144047545","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}