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Embryonic stem cell related gene regulates alternative splicing of transcription factor 3 to maintain human embryonic stem cells' self-renewal and pluripotency. ESRG 可调控 TCF3 的替代剪接,以维持 hESCs 的自我更新和多能性。
IF 4 2区 医学
STEM CELLS Pub Date : 2024-06-14 DOI: 10.1093/stmcls/sxae020
Wen Xie, Weidong Liu, Lei Wang, Shasha Li, Zilin Liao, Hongjuan Xu, Yihan Li, Xingjun Jiang, Caiping Ren
{"title":"Embryonic stem cell related gene regulates alternative splicing of transcription factor 3 to maintain human embryonic stem cells' self-renewal and pluripotency.","authors":"Wen Xie, Weidong Liu, Lei Wang, Shasha Li, Zilin Liao, Hongjuan Xu, Yihan Li, Xingjun Jiang, Caiping Ren","doi":"10.1093/stmcls/sxae020","DOIUrl":"10.1093/stmcls/sxae020","url":null,"abstract":"<p><p>Exploring the mechanism of self-renewal and pluripotency maintenance of human embryonic stem cells (hESCs) is of great significance in basic research and clinical applications, but it has not been fully elucidated. Long non-coding RNAs (lncRNAs) have been shown to play a key role in the self-renewal and pluripotency maintenance of hESCs. We previously reported that the lncRNA ESRG, which is highly expressed in undifferentiated hESCs, can maintain the self-renewal and pluripotency of hPSCs. RNA pull-down mass spectrometry showed that ESRG could bind to other proteins, among which heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) attracted our attention. In this study, we showed that HNRNPA1 can maintain self-renewal and pluripotency of hESCs. ESRG bound to and stabilized HNRNPA1 protein through the ubiquitin-proteasome pathway. In addition, knockdown of ESRG or HNRNPA1 resulted in alternative splicing of TCF3, which originally and primarily encoded E12, to mainly encode E47 and inhibit CDH1 expression. HNRNPA1 could rescue the biological function changes of hESCs caused by ESRG knockdown or overexpression. Our results suggest that ESRG regulates the alternative splicing of TCF3 to affect CDH1 expression and maintain hESCs self-renewal and pluripotency by binding and stabilizing HNRNPA1 protein. This study lays a good foundation for exploring the new molecular regulatory mechanism by which ESRG maintains hESCs self-renewal and pluripotency.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"540-553"},"PeriodicalIF":4.0,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139929260","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}
引用次数: 0
Organoid-based personalized medicine: from tumor outcome prediction to autologous transplantation. 基于类器官的个性化医疗:从肿瘤结果预测到自体移植。
IF 5.2 2区 医学
STEM CELLS Pub Date : 2024-06-14 DOI: 10.1093/stmcls/sxae023
Abel Soto-Gamez, Jeremy P Gunawan, Lara Barazzuol, Sarah Pringle, Rob P Coppes
{"title":"Organoid-based personalized medicine: from tumor outcome prediction to autologous transplantation.","authors":"Abel Soto-Gamez, Jeremy P Gunawan, Lara Barazzuol, Sarah Pringle, Rob P Coppes","doi":"10.1093/stmcls/sxae023","DOIUrl":"10.1093/stmcls/sxae023","url":null,"abstract":"<p><p>Inter-individual variation largely influences disease susceptibility, as well as response to therapy. In a clinical context, the optimal treatment of a disease should consider inter-individual variation and formulate tailored decisions at an individual level. In recent years, emerging organoid technologies promise to capture part of an individual's phenotypic variability and prove helpful in providing clinically relevant molecular insights. Organoids are stem cell-derived 3-dimensional models that contain multiple cell types that can self-organize and give rise to complex structures mimicking the organization and functionality of the tissue of origin. Organoids therefore represent a more faithful recapitulation of the dynamics of the tissues of interest, compared to conventional monolayer cultures, thus supporting their use in evaluating disease prognosis, or as a tool to predict treatment outcomes. Additionally, the individualized nature of patient-derived organoids enables the use of autologous organoids as a source of transplantable material not limited by histocompatibility. An increasing amount of preclinical evidence has paved the way for clinical trials exploring the applications of organoid-based technologies, some of which are in phase I/II. This review focuses on the recent progress concerning the use of patient-derived organoids in personalized medicine, including (1) diagnostics and disease prognosis, (2) treatment outcome prediction to guide therapeutic advice, and (3) organoid transplantation or cell-based therapies. We discuss examples of these potential applications and the challenges associated with their future implementation.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"499-508"},"PeriodicalIF":5.2,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11177156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140206023","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}
引用次数: 0
S-Adenosyl-l-Methionine Alleviates the Senescence of MSCs Through the PI3K/AKT/FOXO3a Signaling Pathway. S-腺苷-L-蛋氨酸通过 PI3K/AKT/FOXO3a 信号通路缓解间充质干细胞的衰老。
IF 4 2区 医学
STEM CELLS Pub Date : 2024-05-15 DOI: 10.1093/stmcls/sxae010
Lipeng Shang, Xiaoxia Li, Xiaoyan Ding, Guoxiang Liu, Zhen Pan, Xiangyan Chen, Yuelei Wang, Bing Li, Ting Wang, Robert Chunhua Zhao
{"title":"S-Adenosyl-l-Methionine Alleviates the Senescence of MSCs Through the PI3K/AKT/FOXO3a Signaling Pathway.","authors":"Lipeng Shang, Xiaoxia Li, Xiaoyan Ding, Guoxiang Liu, Zhen Pan, Xiangyan Chen, Yuelei Wang, Bing Li, Ting Wang, Robert Chunhua Zhao","doi":"10.1093/stmcls/sxae010","DOIUrl":"10.1093/stmcls/sxae010","url":null,"abstract":"<p><p>Cellular senescence significantly affects the proliferative and differentiation capacities of mesenchymal stem cells (MSCs). Identifying key regulators of senescence and exploring potential intervention strategies, including drug-based approaches, are active areas of research. In this context, S-adenosyl-l-methionine (SAM), a critical intermediate in sulfur amino acid metabolism, emerges as a promising candidate for mitigating MSC senescence. In a hydrogen peroxide-induced MSC aging model (100 μM for 2 hours), SAM (50 and 100 μM) was revealed to alleviate the senescence of MSCs, and also attenuated the level of reactive oxygen species and enhanced the adipogenic and osteogenic differentiation in senescent MSCs. In a premature aging mouse model (subcutaneously injected with 150 mg/kg/day d-galactose in the neck and back for 7 weeks), SAM (30 mg/kg/day by gavage for 5 weeks) was shown to delay the overall aging process while increasing the number and thickness of bone trabeculae in the distal femur. Mechanistically, activation of PI3K/AKT signaling and increased phosphorylation of forkhead box O3 (FOXO3a) was proved to be associated with the antisenescence role of SAM. These findings highlight that the PI3K/AKT/FOXO3a axis in MSCs could play a crucial role in MSCs senescence and suggest that SAM may be a potential therapeutic drug for MSCs senescence and related diseases.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"475-490"},"PeriodicalIF":4.0,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140011787","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}
引用次数: 0
Mesenchymal Stromal/Stem Cells Know Best: The Remarkable Complexities of Its Interactions With Polymorphonuclear Neutrophils. 间充质基质/干细胞(MSCs)最清楚:它与多形核中性粒细胞(PMNs)的相互作用异常复杂。
IF 5.2 2区 医学
STEM CELLS Pub Date : 2024-05-15 DOI: 10.1093/stmcls/sxae011
Li-Tzu Wang, Wei Lee, Ko-Jiunn Liu, Huey-Kang Sytwu, Men-Luh Yen, B Linju Yen
{"title":"Mesenchymal Stromal/Stem Cells Know Best: The Remarkable Complexities of Its Interactions With Polymorphonuclear Neutrophils.","authors":"Li-Tzu Wang, Wei Lee, Ko-Jiunn Liu, Huey-Kang Sytwu, Men-Luh Yen, B Linju Yen","doi":"10.1093/stmcls/sxae011","DOIUrl":"10.1093/stmcls/sxae011","url":null,"abstract":"<p><p>Polymorphonuclear neutrophils (PMNs), the predominant immune cell type in humans, have long been known as first-line effector cells against bacterial infections mainly through phagocytosis and production of reactive oxygen species (ROS). However, recent research has unveiled novel and pivotal roles of these abundant but short-lived granulocytes in health and disease. Human mesenchymal stromal/stem cells (MSCs), renowned for their regenerative properties and modulation of T lymphocytes from effector to regulatory phenotypes, exhibit complex and context-dependent interactions with PMNs. Regardless of species or source, MSCs strongly abrogate PMN apoptosis, a critical determinant of PMN function, except if PMNs are highly stimulated. MSCs also have the capacity to fine-tune PMN activation, particularly in terms of CD11b expression and phagocytosis. Moreover, MSCs can modulate numerous other PMN functions, spanning migration, ROS production, and neutrophil extracellular trap (NET) formation/NETosis, but directionality is remarkably dependent on the underlying context: in normal nondiseased conditions, MSCs enhance PMN migration and ROS production, whereas in inflammatory conditions, MSCs reduce both these functions and NETosis. Furthermore, the state of the MSCs themselves, whether isolated from diseased or healthy donors, and the specific secreted products and molecules, can impact interactions with PMNs; while healthy MSCs prevent PMN infiltration and NETosis, MSCs isolated from patients with cancer promote these functions. This comprehensive analysis highlights the intricate interplay between PMNs and MSCs and its profound relevance in healthy and pathological conditions, shedding light on how to best strategize the use of MSCs in the expanding list of diseases with PMN involvement.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"403-415"},"PeriodicalIF":5.2,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139680447","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}
引用次数: 0
HucMSCs Delay Muscle Atrophy After Peripheral Nerve Injury Through Exosomes by Repressing Muscle-Specific Ubiquitin Ligases. HucMSCs 通过外泌体抑制肌肉特异性泛素连接酶,从而延缓周围神经损伤后的肌肉萎缩。
IF 4 2区 医学
STEM CELLS Pub Date : 2024-05-15 DOI: 10.1093/stmcls/sxae017
Jian Chen, Yaqiong Zhu, Hui Gao, Xianghui Chen, Dan Yi, MoLin Li, Li Wang, Guanhui Xing, Siming Chen, Jie Tang, Yuexiang Wang
{"title":"HucMSCs Delay Muscle Atrophy After Peripheral Nerve Injury Through Exosomes by Repressing Muscle-Specific Ubiquitin Ligases.","authors":"Jian Chen, Yaqiong Zhu, Hui Gao, Xianghui Chen, Dan Yi, MoLin Li, Li Wang, Guanhui Xing, Siming Chen, Jie Tang, Yuexiang Wang","doi":"10.1093/stmcls/sxae017","DOIUrl":"10.1093/stmcls/sxae017","url":null,"abstract":"<p><p>Cell therapy based on mesenchymal stem cells (MSCs) alleviate muscle atrophy caused by diabetes and aging; however, the impact of human umbilical cord mesenchymal stem cells on muscle atrophy following nerve injury and the underlying mechanisms remain unclear. In this study, we evaluated the therapeutic efficacy of human umbilical cord MSCs (hucMSCs) and hucMSC-derived exosomes (hucMSC-EXOs) for muscle atrophy following nerve injury and identified the underlying molecular mechanisms. Sciatic nerve crush injury in rats and the induction of myotubes in L6 cells were used to determine the ameliorating effect of hucMSCs and hucMSC-EXOs on muscle atrophy. Q-PCR and Western blot analyses were used to measure the expression of muscle-specific ubiquitin ligases Fbxo32 (Atrogin1, MAFbx) and Trim63 (MuRF-1). Dual-luciferase reporter gene experiments were conducted to validate the direct binding of miRNAs to their target genes. Local injection of hucMSCs and hucMSC-EXOs mitigated atrophy in the rat gastrocnemius muscle following sciatic nerve crush injury. In vitro, hucMSC-EXOs alleviated atrophy in L6 myotubes. Mechanistic analysis indicated the upregulation of miR-23b-3p levels in L6 myotubes following hucMSC-EXOs treatment. MiR-23b-3p significantly inhibited the expression of its target genes, Fbxo32 and Trim63, and suppressed myotube atrophy. Notably, an miR-23b-3p inhibitor reversed the inhibitory effect of miR-23b-3p on myotube atrophy in vitro. These results suggest that hucMSCs and their exosomes alleviate muscle atrophy following nerve injury. MiR-23b-3p in exosomes secreted by hucMSCs contributes to this mechanism by inhibiting the muscle-specific ubiquitination ligases Fbxo32 and Trim63.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"460-474"},"PeriodicalIF":4.0,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11094387/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139929261","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}
引用次数: 0
Uterine Immunoprivileged Cells Restore Cardiac Function of Male Recipients After Myocardial Infarction. 子宫免疫细胞可恢复心肌梗塞后男性受体的心脏功能。
IF 5.2 2区 医学
STEM CELLS Pub Date : 2024-05-15 DOI: 10.1093/stmcls/sxae008
Zexu Peng, Ana Ludke, Jun Wu, Shuhong Li, Faisal J Alibhai, Yichong Zhang, Yunfei Fan, Huifang Song, Sheng He, Jun Xie, Ren-Ke Li
{"title":"Uterine Immunoprivileged Cells Restore Cardiac Function of Male Recipients After Myocardial Infarction.","authors":"Zexu Peng, Ana Ludke, Jun Wu, Shuhong Li, Faisal J Alibhai, Yichong Zhang, Yunfei Fan, Huifang Song, Sheng He, Jun Xie, Ren-Ke Li","doi":"10.1093/stmcls/sxae008","DOIUrl":"10.1093/stmcls/sxae008","url":null,"abstract":"<p><p>It has been documented that the uterus plays a key cardio-protective role in pre-menopausal women, which is supported by uterine cell therapy, to preserve cardiac functioning post-myocardial infarction, being effective among females. However, whether such therapies would also be beneficial among males is still largely unknown. In this study, we aimed to fill in this gap in knowledge by examining the effects of transplanted uterine cells on infarcted male hearts. We identified, based on major histocompatibility complex class I (MHC-I) expression levels, 3 uterine reparative cell populations: MHC-I(neg), MHC-I(mix), and MHC-I(pos). In vitro, MHC-I(neg) cells showed higher levels of pro-angiogenic, pro-survival, and anti-inflammatory factors, compared to MHC-I(mix) and MHC-I(pos). Furthermore, when cocultured with allogeneic mixed leukocytes, MHC-I(neg) had lower cytotoxicity and leukocyte proliferation. In particular, CD8+ cytotoxic T cells significantly decreased, while CD4+CD25+ Tregs and CD4-CD8- double-negative T cells significantly increased when cocultured with MHC-I(neg), compared to MHC-I(mix) and MHC-I(pos) cocultures. In vivo, MHC-I(neg) as well as MHC-I(mix) were found under both syngeneic and allogeneic transplantation in infarcted male hearts, to significantly improve cardiac function and reduce the scar size, via promoting angiogenesis in the infarcted area. All of these findings thus support the view that males could also benefit from the cardio-protective effects observed among females, via cell therapy approaches involving the transplantation of immuno-privileged uterine reparative cells in infarcted hearts.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"430-444"},"PeriodicalIF":5.2,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139519411","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}
引用次数: 0
MSC-Derived Small Extracellular Vesicles Exert Cardioprotective Effect Through Reducing VLCFAs and Apoptosis in Human Cardiac Organoid IRI Model. 间充质干细胞衍生的细胞外小泡通过减少VLCFAs和细胞凋亡在人心脏器质性IRI模型中发挥心脏保护作用
IF 5.2 2区 医学
STEM CELLS Pub Date : 2024-05-15 DOI: 10.1093/stmcls/sxae015
Boon Min Poh, Lee Chuen Liew, Yan Ni Annie Soh, Ruenn Chai Lai, Sai Kiang Lim, Ying Swan Ho, Boon Seng Soh
{"title":"MSC-Derived Small Extracellular Vesicles Exert Cardioprotective Effect Through Reducing VLCFAs and Apoptosis in Human Cardiac Organoid IRI Model.","authors":"Boon Min Poh, Lee Chuen Liew, Yan Ni Annie Soh, Ruenn Chai Lai, Sai Kiang Lim, Ying Swan Ho, Boon Seng Soh","doi":"10.1093/stmcls/sxae015","DOIUrl":"10.1093/stmcls/sxae015","url":null,"abstract":"<p><p>Cardiovascular diseases (CVDs) are the leading cause of death worldwide, accounting for 31% of all deaths globally. Myocardial ischemia-reperfusion injury (IRI), a common complication of CVDs, is a major cause of mortality and morbidity. Studies have shown efficacious use of mesenchymal stem cells-derived small extracellular vesicles (MSCs-EVs) to mitigate IRI in animals, but few research has been done on human-related models. In this study, human embryonic stem cell-derived chambered cardiac organoid (CCO) was used as a model system to study the effects of MSC-EVs on myocardial IRI. The results revealed that MSC-EVs treatment reduced apoptosis and improved contraction resumption of the CCOs. Metabolomics analysis showed that this effect could be attributed to EVs' ability to prevent the accumulation of unsaturated very long-chain fatty acids (VLCFAs). This was corroborated when inhibition of fatty acid synthase, which was reported to reduce VLCFAs, produced a similar protective effect to EVs. Overall, this study uncovered the mechanistic role of MSC-EVs in mitigating IRI that involves preventing the accumulation of unsaturated VLCFA, decreasing cell death, and improving contraction resumption in CCOs.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"416-429"},"PeriodicalIF":5.2,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139929262","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}
引用次数: 0
Human Umbilical Cord Mesenchymal Stromal Cell-Derived Exosomes Alleviate Hypoxia-Induced Pulmonary Arterial Hypertension in Mice Via Macrophages. 人脐带间充质基质细胞衍生的外泌体可通过巨噬细胞缓解缺氧诱发的小鼠肺动脉高压。
IF 5.2 2区 医学
STEM CELLS Pub Date : 2024-04-15 DOI: 10.1093/stmcls/sxad098
Hong Liu, Qingqing Zhang, Chuanchuan Liu, Yuwei Zhang, Yuxiang Wang, Pan Huang, Lan Ma, Rili Ge
{"title":"Human Umbilical Cord Mesenchymal Stromal Cell-Derived Exosomes Alleviate Hypoxia-Induced Pulmonary Arterial Hypertension in Mice Via Macrophages.","authors":"Hong Liu, Qingqing Zhang, Chuanchuan Liu, Yuwei Zhang, Yuxiang Wang, Pan Huang, Lan Ma, Rili Ge","doi":"10.1093/stmcls/sxad098","DOIUrl":"10.1093/stmcls/sxad098","url":null,"abstract":"<p><p>Pulmonary hypertension (PH) is an intractable, severe, and progressive cardiopulmonary disease. Recent findings suggest that human umbilical cord mesenchymal stromal cells (HUCMSCs) and HUCMSC-derived exosomes (HUCMSC-Exos) possess potential therapeutic value for PH. However, whether they have beneficial effects on hypoxic pulmonary hypertension (HPH) is unclear. Exos are released into the extracellular environment by the fusion of intracellular multivesicular bodies with the cell membrane, and they play an important role in cellular communication. Exos ameliorate immune inflammation levels, alter macrophage phenotypes, regulate mitochondrial metabolic function, and inhibit pulmonary vascular remodeling, thereby improving PH. Macrophages are important sources of cytokines and other transmitters and can promote the release of cytokines, vasoactive molecules, and reactive oxygen species, all of which are associated with pulmonary vascular remodeling. Therefore, the aim of this study was to investigate whether HUCMSC-Exos could improve the lung inflammatory microenvironment and inhibit pulmonary vascular remodeling by targeting macrophages and identifying the underlying mechanisms. The results showed that HUCMSC-Exos promoted M2 macrophage polarization, decreased pro-inflammatory factors, increased IL-10 levels, and inhibited IL-33/ST2 axis expression, thereby inhibiting hypoxia-induced proliferation of pulmonary artery smooth muscle cells and ameliorating HPH.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"329-345"},"PeriodicalIF":5.2,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139058054","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}
引用次数: 0
Fructose Potentiates Bone Loss and Marrow Adipose Tissue Accumulation by Inhibiting Adenosine 5'-Monophosphate-Activated Protein Kinase in Mesenchymal Stem Cells. 果糖通过抑制间充质干细胞中的 5'-Monophosphate-Activated Protein Kinase 促成骨质流失和骨髓脂肪组织的积累
IF 5.2 2区 医学
STEM CELLS Pub Date : 2024-04-15 DOI: 10.1093/stmcls/sxae001
Ziqi Yan, Juan Du, Rui Zhao, Xu Liu, Junji Xu, Lijia Guo, Yi Liu
{"title":"Fructose Potentiates Bone Loss and Marrow Adipose Tissue Accumulation by Inhibiting Adenosine 5'-Monophosphate-Activated Protein Kinase in Mesenchymal Stem Cells.","authors":"Ziqi Yan, Juan Du, Rui Zhao, Xu Liu, Junji Xu, Lijia Guo, Yi Liu","doi":"10.1093/stmcls/sxae001","DOIUrl":"10.1093/stmcls/sxae001","url":null,"abstract":"<p><p>Increased fructose consumption has been elucidated to contribute to metabolic diseases. Bone is a dynamic organ that undergoes constant remodeling. However, the effects of fructose on bone health are still in dispute. Here, we identified fructose deteriorated bone mineral density while promoting the abundance of bone marrow adipose tissue. Fructose remarkably promoted the bone marrow mesenchymal stem cells' (BMMSCs) adipogenic commitment at the expense of osteogenic commitment. Fructose boosted the glycolysis of BMMSCs and inhibited phosphorylation of adenosine 5'-monophosphate-activated protein kinase (AMPK), which played a crucial role in bone-fat alteration. Our results suggested that fructose potentiated bone loss and marrow adipose tissue accumulation by suppressing AMPK activation in BMMSCs. Understanding fructose which affected bone metabolism was thus of primary importance in order to establish preventative measures or treatments for this condition.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"374-384"},"PeriodicalIF":5.2,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139568780","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}
引用次数: 0
TNFAIP3 Derived from Skeletal Stem Cells Alleviated Rat Osteoarthritis by Inhibiting the Necroptosis of Subchondral Osteoblasts. 骨骼干细胞提取的 TNFAIP3 可抑制软骨下成骨细胞的坏死,从而缓解大鼠骨关节炎。
IF 5.2 2区 医学
STEM CELLS Pub Date : 2024-04-15 DOI: 10.1093/stmcls/sxad097
Xiao-Tong Li, Zhi-Ling Li, Pei-Lin Li, Fei-Yan Wang, Xiao-Yu Zhang, Yu-Xing Wang, Zhi-Dong Zhao, Bo-Feng Yin, Rui-Cong Hao, Ning Mao, Wen-Rong Xia, Li Ding, Heng Zhu
{"title":"TNFAIP3 Derived from Skeletal Stem Cells Alleviated Rat Osteoarthritis by Inhibiting the Necroptosis of Subchondral Osteoblasts.","authors":"Xiao-Tong Li, Zhi-Ling Li, Pei-Lin Li, Fei-Yan Wang, Xiao-Yu Zhang, Yu-Xing Wang, Zhi-Dong Zhao, Bo-Feng Yin, Rui-Cong Hao, Ning Mao, Wen-Rong Xia, Li Ding, Heng Zhu","doi":"10.1093/stmcls/sxad097","DOIUrl":"10.1093/stmcls/sxad097","url":null,"abstract":"<p><p>Recent investigations have shown that the necroptosis of tissue cells in joints is important in the development of osteoarthritis (OA). This study aimed to investigate the potential effects of exogenous skeletal stem cells (SSCs) on the necroptosis of subchondral osteoblasts in OA. Human SSCs and subchondral osteoblasts isolated from human tibia plateaus were used for Western blotting, real-time PCR, RNA sequencing, gene editing, and necroptosis detection assays. In addition, the rat anterior cruciate ligament transection OA model was used to evaluate the effects of SSCs on osteoblast necroptosis in vivo. The micro-CT and pathological data showed that intra-articular injections of SSCs significantly improved the microarchitecture of subchondral trabecular bones in OA rats. Additionally, SSCs inhibited the necroptosis of subchondral osteoblasts in OA rats and necroptotic cell models. The results of bulk RNA sequencing of SSCs stimulated or not by tumor necrosis factor α suggested a correlation of SSCs-derived tumor necrosis factor α-induced protein 3 (TNFAIP3) and cell necroptosis. Furthermore, TNFAIP3-derived from SSCs contributed to the inhibition of the subchondral osteoblast necroptosis in vivo and in vitro. Moreover, the intra-articular injections of TNFAIP3-overexpressing SSCs further improved the subchondral trabecular bone remodeling of OA rats. Thus, we report that TNFAIP3 from SSCs contributed to the suppression of the subchondral osteoblast necroptosis, which suggests that necroptotic subchondral osteoblasts in joints may be possible targets to treat OA by stem cell therapy.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"360-373"},"PeriodicalIF":5.2,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139047856","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}
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