STEM CELLS最新文献

{"title":"Long noncoding RNA UCA1 promotes the chondrogenic differentiation of human bone marrow mesenchymal stem cells via regulating PARP1 ubiquitination.","authors":"Tao Shu, Jiachun Li, Juyuan Gu, Liang Wu, Peng Xie, Dongfeng Zhang, Wen Li, Junming Wan, Xiaozuo Zheng","doi":"10.1093/stmcls/sxae038","DOIUrl":"10.1093/stmcls/sxae038","url":null,"abstract":"<p><p>Bone marrow mesenchymal stem cells (BMSCs) possess the potential to differentiate into cartilage cells. Long noncoding RNA (lncRNAs) urothelial carcinoma associated 1 (UCA1) has been confirmed to improve the chondrogenic differentiation of marrow mesenchymal stem cells (MSCs). Herein, we further investigated the effects and underlying mechanisms of these processes. The expression of UCA1 was positively associated with chondrogenic differentiation and the knockdown of UCA1 has been shown to attenuate the expression of chondrogenic markers. RNA pull-down assay and RNA immunoprecipitation showed that UCA1 could directly bind to PARP1 protein. UCA1 could improve PARP1 protein via facilitating USP9X-mediated PARP1 deubiquitination. Then these processes stimulated the NF-κB signaling pathway. In addition, PARP1 was declined in UCA1 knockdown cells, and silencing of PARP1 could diminish the increasing effects of UCA1 on the chondrogenic differentiation from MSCs and signaling pathway activation. Collectively, these outcomes suggest that UCA1 could act as a mediator of PARP1 protein ubiquitination and develop the chondrogenic differentiation of MSCs.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"752-762"},"PeriodicalIF":4.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141198694","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":"Vascular endothelial growth factor secretion and immunosuppression are distinct potency mechanisms of human bone marrow mesenchymal stromal cells.","authors":"Tyler U Faircloth, Sara Temple, Rhett N Parr, Anna B Tucker, Devi Rajan, Peiman Hematti, Subra Kugathasan, Raghavan Chinnadurai","doi":"10.1093/stmcls/sxae040","DOIUrl":"10.1093/stmcls/sxae040","url":null,"abstract":"<p><p>Mesenchymal stromal cells (MSCs) are investigated as cellular therapeutics for inflammatory bowel diseases and associated perianal fistula, although consistent efficacy remains a concern. Determining host factors that modulate MSCs' potency including their secretion of angiogenic and wound-healing factors, immunosuppression, and anti-inflammatory properties are important determinants of their functionality. We investigated the mechanisms that regulate the secretion of angiogenic and wound-healing factors and immune suppression of human bone marrow MSCs. Secretory analysis of MSCs focusing on 18 angiogenic and wound-healing secretory molecules identified the most abundancy of vascular endothelial growth factor A (VEGF-A). MSC viability and secretion of other angiogenic factors are not dependent on VEGF-A secretion which exclude the autocrine role of VEGF-A on MSC's fitness. However, the combination of inflammatory cytokines IFNγ and TNFα reduces MSC's VEGF-A secretion. To identify the effect of intestinal microvasculature on MSCs' potency, coculture analysis was performed between human large intestine microvascular endothelial cells (HLMVECs) and human bone marrow-derived MSCs. HLMVECs do not attenuate MSCs' viability despite blocking their VEGF-A secretion. In addition, HLMVECs neither attenuate MSC's IFNγ mediated upregulation of immunosuppressive enzyme indoleamine 2,3-dioxygenase nor abrogate suppression of T-cell proliferation despite the attenuation of VEGF-A secretion. We found that HLMVECs express copious amounts of endothelial nitric oxide synthase and mechanistic analysis showed that pharmacological blocking reverses HLMVEC-mediated attenuation of MSC's VEGF-A secretion. Together these results suggest that secretion of VEGF-A and immunosuppression are separable functions of MSCs which are regulated by distinct mechanisms in the host.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"736-751"},"PeriodicalIF":4.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141198702","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":"Correction to: Tcf12, A Member of Basic Helix-Loop-Helix Transcription Factors, Mediates Bone Marrow Mesenchymal Stem Cell Osteogenic Differentiation In Vitro and In Vivo.","authors":"","doi":"10.1093/stmcls/sxae036","DOIUrl":"10.1093/stmcls/sxae036","url":null,"abstract":"","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"777-778"},"PeriodicalIF":4.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141074481","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":"Tibetan mesenchymal stem cell-derived exosomes alleviate pulmonary vascular remodeling in hypoxic pulmonary hypertension rats.","authors":"Qingqing Zhang, Hong Liu, Chuanchuan Liu, Yuxiang Wang, Pan Huang, Xiaobo Wang, Yougang Ma, Lan Ma, Rili Ge","doi":"10.1093/stmcls/sxae032","DOIUrl":"10.1093/stmcls/sxae032","url":null,"abstract":"<p><p>Hypoxic pulmonary hypertension (HPH) is characterized by progressive pulmonary vasoconstriction, vascular remodeling, and right ventricular hypertrophy, causing right heart failure. This study aimed to investigate the therapeutic effects of exosomes from Tibetan umbilical cord mesenchymal stem cells on HPH via the TGF-β1/Smad2/3 pathway, comparing them with exosomes from Han Chinese individuals. An HPH rat model was established in vivo, and a hypoxia-induced injury in the rat pulmonary artery smooth muscle cells (rPASMCs) was simulated in vitro. Exosomes from human umbilical cord mesenchymal stem cells were administered to HPH model rats or added to cultured rPASMCs. The therapeutic effects of Tibetan-mesenchymal stem cell-derived exosomes (Tibetan-MSC-exo) and Han-mesenchymal stem cell-derived exosomes (Han-MSC-exo) on HPH were investigated through immunohistochemistry, western blotting, EdU, and Transwell assays. The results showed that Tibetan-MSC-exo significantly attenuated pulmonary vascular remodeling and right ventricular hypertrophy in HPH rats compared with Han-MSC-exo. Tibetan-MSC-exo demonstrated better inhibition of hypoxia-induced rPASMCs proliferation and migration. Transcriptome sequencing revealed upregulated genes (Nbl1, Id2, Smad6, and Ltbp1) related to the TGFβ pathway. Nbl1 knockdown enhanced hypoxia-induced rPASMCs proliferation and migration, reversing Tibetan-MSC-exo-induced downregulation of TGFβ1 and p-Smad2/3. Furthermore, TGFβ1 overexpression hindered the therapeutic effects of Tibetan-MSC-exo and Han-MSC-exo on hypoxic injury. These findings suggest that Tibetan-MSC-exo favors HPH treatment better than Han-MSC-exo, possibly through the modulation of the TGFβ1/Smad2/3 pathway via Nbl1.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"720-735"},"PeriodicalIF":4.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140875390","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":"Amphiregulin secreted by umbilical cord multipotent stromal cells protects against ferroptosis of macrophages via the activating transcription factor 3-CD36 axis to alleviate endometrial fibrosis.","authors":"Jiali Wang, Jingman Li, Shuangan Wang, Yuchen Pan, Jingjing Yang, Lijie Yin, Huan Dou, Yayi Hou","doi":"10.1093/stmcls/sxae035","DOIUrl":"10.1093/stmcls/sxae035","url":null,"abstract":"<p><p>Endometrium fibrosis is the leading cause of uterine infertility. Macrophages participated in the occurrence and development of endometrial fibrosis. We previously reported that human umbilical cord multipotent stromal cells (hUC-MSCs) exerted their therapeutic effect in a macrophage-dependent manner in endometrial fibrosis. However precise mechanisms by which hUC-MSCs may influence macrophages in endometrial fibrosis remain largely unexplored. Here, we demonstrated that abnormal iron and lipid metabolism occurred in patients with intrauterine adhesions (IUA) and murine models. Ferroptosis has been proven to contribute to the progression of fibrotic diseases. Our results revealed that pharmacological activation of ferroptosis by Erastin aggravated endometrial fibrosis, while inhibition of ferroptosis by Ferrostatin-1 ameliorated endometrial fibrosis in vivo. Moreover, ferroptosis of macrophages was significantly upregulated in endometria of IUA murine models. Of note, transcriptome profiles revealed that CD36 gene expression was significantly increased in patients with IUA and immunofluorescence analysis showed CD36 protein was mainly located in macrophages. Silencing CD36 in macrophages could reverse cell ferroptosis. Dual luciferase reporter assay revealed that CD36 was the direct target of activation transcription factor 3 (ATF3). Furthermore, through establishing coculture system and IUA murine models, we found that hUC-MSCs had a protective role against macrophage ferroptosis and alleviated endometrial fibrosis related to decreased CD36 and ATF3. The effect of hUC-MSCs on macrophage ferroptosis was attributed to the upregulation of amphiregulin (AREG). Our data highlighted that macrophage ferroptosis occurred in endometrial fibrosis via the ATF3-CD36 pathway and hUC-MSCs protected against macrophage ferroptosis to alleviate endometrial fibrosis via secreting AREG. These findings provided a potential target for therapeutic implications of endometrial fibrosis.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"763-776"},"PeriodicalIF":4.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140907676","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":"Empagliflozin Ameliorates the Impaired Osteogenic Differentiation Ability of Adipose-Derived Stem Cells in Diabetic Osteoporosis by Activating Autophagy.","authors":"Shuanglin Yang, Ya Lin, Yuping Xie, Ting Fu, Tianli Wu, Xiaorong Lan, Fangzhi Lou, Jingang Xiao","doi":"10.1093/stmcls/sxae019","DOIUrl":"10.1093/stmcls/sxae019","url":null,"abstract":"<p><p>Adipose-derived stem cells (ASCs) from diabetic osteoporosis (DOP) mice showed impaired osteogenic differentiation capacity. Recent studies have shown that in addition to antidiabetic drugs, sodium-glucose co-transporter inhibitor-2 (SGLT-2), empagliflozin, can play multipotent roles through various mechanisms of action. In this study, we aimed to investigate the effects and underlying mechanisms of empagliflozin on osteogenic differentiation of ASCs in DOP mice. Our results showed that osteogenic differentiation potential and autophagy activity weakened in DOP-ASCs when compared to controls. However, empagliflozin enhanced autophagy flux by promoting the formation of autophagosomes and acidification of autophagic lysosomes, resulting in an increase in LC3-II expression and a decrease in SQSTM1 expression. Furthermore, empagliflozin contributed to the reversal of osteogenesis inhibition in DOP-ASCs induced by a diabetic microenvironment. When 3-methyladenine was used to block autophagy activity, empagliflozin could not exert its protective effect on DOP-ASCs. Nonetheless, this study demonstrated that the advent of cellular autophagy attributed to the administration of empagliflozin could ameliorate the impaired osteogenic differentiation potential of ASCs in DOP mice. This finding might be conducive to the application of ASCs transplantation for promoting bone fracture healing and bone regeneration in patients with DOP.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"623-635"},"PeriodicalIF":4.0,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139929259","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":"Expression of Concern: Therapeutic Efficacy and Fate of Bimodal Engineered Stem Cells in Malignant Brain Tumors.","authors":"","doi":"10.1093/stmcls/sxae012","DOIUrl":"10.1093/stmcls/sxae012","url":null,"abstract":"","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"675"},"PeriodicalIF":4.0,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139690858","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":"Expression of Concern: Stem Cells Engineered During Different Stages of Reprogramming Reveal Varying Therapeutic Efficacies.","authors":"","doi":"10.1093/stmcls/sxae014","DOIUrl":"10.1093/stmcls/sxae014","url":null,"abstract":"","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"676"},"PeriodicalIF":4.0,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139690857","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":"Arp2/3 mediated dynamic lamellipodia of the hPSC colony edges promote liposome-based DNA delivery.","authors":"Michelle Surma, Kavitha Anbarasu, Arupratan Das","doi":"10.1093/stmcls/sxae033","DOIUrl":"10.1093/stmcls/sxae033","url":null,"abstract":"<p><p>Cationic liposome-mediated delivery of drugs, DNA, or RNA plays a pivotal role in small molecule therapy, gene editing, and immunization. However, our current knowledge regarding the cellular structures that facilitate this process remains limited. Here, we used human pluripotent stem cells (hPSCs), which form compact colonies consisting of dynamically active cells at the periphery and epithelial-like cells at the core. We discovered that cells at the colony edges selectively got transfected by cationic liposomes through actin-related protein 2/3 (Arp2/3) dependent dynamic lamellipodia, which is augmented by myosin II inhibition. Conversely, cells at the core establish tight junctions at their apical surfaces, impeding liposomal access to the basal lamellipodia and thereby inhibiting transfection. In contrast, liposomes incorporating mannosylated lipids are internalized throughout the entire colony via receptor-mediated endocytosis. These findings contribute a novel mechanistic insight into enhancing therapeutic delivery via liposomes, particularly in cell types characterized by dynamic lamellipodia, such as immune cells or those comprising the epithelial layer.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"607-622"},"PeriodicalIF":4.0,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11228622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140890827","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":"Protein Crotonylation Promotes Osteogenic Differentiation of Periodontal Ligament Stem Cells via the PI3K-AKT Pathway.","authors":"Ruohui Han, Rui Dang, Fan Liu, Shaochen Nie, Shaofei Tao, Liangyu Xing, Tianle Yang, Meilin Hu, Dayong Liu","doi":"10.1093/stmcls/sxae018","DOIUrl":"10.1093/stmcls/sxae018","url":null,"abstract":"<p><p>Posttranslational modifications (PTMs) are crucial regulatory mechanisms for cellular differentiation and organismal development. Acylation modification is one of the main PTMs that plays a pivotal role in regulating the osteogenic differentiation of mesenchymal stem cells and is a focal point of research in bone tissue regeneration. However, its mechanism remains incompletely understood. This article aims to investigate the impact of protein crotonylation on osteogenic differentiation in periodontal ligament stem cells (PDLSCs) and elucidate its underlying mechanisms. Western blot analysis identified that the modification level of acetylation, crotonylation, and succinylation were significantly upregulated after osteogenic induction of PDLSCs. Subsequently, sodium crotonate (NaCr) was added to the medium and acyl-CoA synthetase short-chain family member 2 (ACSS2) was knocked down by short hairpin RNA plasmids to regulate the total level of protein crotonylation. The results indicated that treatment with NaCr promoted the expression of osteogenic differentiation-related factors in PDLSCs, whereas silencing ACSS2 had the opposite effect. In addition, mass spectrometry analysis was used to investigate the comprehensive analysis of proteome-wide crotonylation in PDLSCs under osteogenic differentiation. The analysis revealed that the level of protein crotonylation related to the PI3K-AKT signaling pathway was significantly upregulated in PDLSCs after osteogenic induction. Treatment with NaCr and silencing ACSS2 affected the activation of the PI3K-AKT signaling pathway. Collectively, our study demonstrates that protein crotonylation promotes osteogenic differentiation of PDLSCs via the PI3K-AKT pathway, providing a novel targeting therapeutic approach for bone tissue regeneration.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"650-661"},"PeriodicalIF":4.0,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139929263","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}