STEM CELLS最新文献_第5页

Advantages of Cell Proliferation and Immune Regulation in CD146+NESTIN+ HUMSCs: Insights from Single-Cell RNA Sequencing. CD146+NESTIN+ HUMSCs 的细胞增殖和免疫调节优势：单细胞 RNA 测序的启示。

IF 4 2区医学

STEM CELLS Pub Date : 2024-10-21 DOI: 10.1093/stmcls/sxae063

Peng Huang, Xiaofei Qin, Chuiqin Fan, Huifeng Zhong, Manna Wang, Fuyi Chen, Maochuan Liao, Nanpeng Zheng, Hongwu Wang, Bingchun Lin, Lian Ma

{"title":"Advantages of Cell Proliferation and Immune Regulation in CD146+NESTIN+ HUMSCs: Insights from Single-Cell RNA Sequencing.","authors":"Peng Huang, Xiaofei Qin, Chuiqin Fan, Huifeng Zhong, Manna Wang, Fuyi Chen, Maochuan Liao, Nanpeng Zheng, Hongwu Wang, Bingchun Lin, Lian Ma","doi":"10.1093/stmcls/sxae063","DOIUrl":"https://doi.org/10.1093/stmcls/sxae063","url":null,"abstract":"The heterogeneity of stem cells is a significant factor inhibiting their clinical application, as different cell subpopulations may exhibit substantial differences in biological functions. We performed single-cell sequencing on HUMSCs from three donors of different gestational ages (22 + 5 weeks, 28 weeks, 39 weeks). We also compared the data with single-cell sequencing data from BMSCs from two public databases. The content of CD146+Nestin+ MSCs in preterm HUMSCs (22 + 5W: 30.2%, 28W: 25.8%) was higher than that in full-term HUMSCs (39W: 0.5%) and BMSCs (BMSC1: 0, BMSC2: 0.9%). Cell cycle analysis indicated a higher proportion of cells in the proliferative G2M phase in CD146+Nestin+ MSCs (40.8%) compared to CD146+Nestin- MSCs (20%) and CD146-Nestin- MSCs (12.5%). Degree of differentiation assessment suggested that CD146+Nestin+ MSCs exhibited lower differentiation than other cell subpopulations. Differential gene analysis revealed that CD146+Nestin+ MSCs overexpressed immune regulation-related factors. GO and KEGG enrichment analysis of modules identified by WGCNA suggested enrichment in pathways related to cellular immune regulation, antimicrobial activity, and proliferation. Immune-related gene analysis indicated that CD146+Nestin+ MSCs exhibited expression of multiple immune-related genes associated with \"Antimicrobials,\" \"Cytokines,\" and \"Cytokine Receptors.\" Gene regulatory network analysis revealed high expression of immune-related regulators RELB, GAPB1, and EHF in CD146+Nestin+ MSCs.Our study provides a single-cell atlas of preterm HUMSCs, demonstrating the expression of CD146+Nestin+ MSCs across different tissues and confirming their advantages in cellular proliferation, antimicrobial activity, immune regulation, and low differentiation at the RNA level. This contributes valuable insights for the clinical application of HUMSCs.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142454402","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

Integrin-linked kinase control dental pulp stem cell senescence via the mTOR signaling pathway. 整合素连接激酶通过 mTOR 信号通路控制牙髓干细胞衰老

IF 4 2区医学

STEM CELLS Pub Date : 2024-10-09 DOI: 10.1093/stmcls/sxae047

Lu Chen, Xiping Wang, Sha Tian, Linxi Zhou, Li Wang, Xiaohan Liu, Zihan Yang, Guiqiang Fu, Xingguang Liu, Chen Ding, Duohong Zou

{"title":"Integrin-linked kinase control dental pulp stem cell senescence via the mTOR signaling pathway.","authors":"Lu Chen, Xiping Wang, Sha Tian, Linxi Zhou, Li Wang, Xiaohan Liu, Zihan Yang, Guiqiang Fu, Xingguang Liu, Chen Ding, Duohong Zou","doi":"10.1093/stmcls/sxae047","DOIUrl":"10.1093/stmcls/sxae047","url":null,"abstract":"Human dental pulp stem cells (HDPSCs) showed an age-dependent decline in proliferation and differentiation capacity. Decline in proliferation and differentiation capacity affects the dental stromal tissue homeostasis and impairs the regenerative capability of HDPSCs. However, which age-correlated proteins regulate the senescence of HDPSCs remain unknown. Our study investigated the proteomic characteristics of HDPSCs isolated from subjects of different ages and explored the molecular mechanism of age-related changes in HDPSCs. Our study showed that the proliferation and osteogenic differentiation of HDPSCs were decreased, while the expression of aging-related genes (p21, p53) and proportion of senescence-associated β-galactosidase (SA-β-gal)-positive cells were increased with aging. The bioinformatic analysis identified that significant proteins positively correlated with age were enriched in response to the mammalian target of rapamycin (mTOR) signaling pathway (ILK, MAPK3, mTOR, STAT1, and STAT3). We demonstrated that OSU-T315, an inhibitor of integrin-linked kinase (ILK), rejuvenated aged HDPSCs, similar to rapamycin (an inhibitor of mTOR). Treatment with OSU-T315 decreased the expression of aging-related genes (p21, p53) and proportion of SA-β-gal-positive cells in HDPSCs isolated from old (O-HDPSCs). Additionally, OSU-T315 promoted the osteoblastic differentiation capacity of O-HDPSCs in vitro and bone regeneration of O-HDPSCs in rat calvarial bone defects model. Our study indicated that the proliferation and osteoblastic differentiation of HDPSCs were impaired with aging. Notably, the ILK/AKT/mTOR/STAT1 signaling pathway may be a major factor in the regulation of HDPSC senescence, which help to provide interventions for HDPSC senescence.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"861-873"},"PeriodicalIF":4.0,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142015888","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

TMEM16A regulates satellite cell-mediated skeletal muscle regeneration by ensuring a moderate level of caspase 3 activity. TMEM16A 通过确保适度的 Caspase 3 活性来调节卫星细胞介导的骨骼肌再生。

IF 4 2区医学

STEM CELLS Pub Date : 2024-10-09 DOI: 10.1093/stmcls/sxae048

Zhiyuan Sun, Xinqi Shan, Chun'e Fan, Lutao Liu, Shuai Li, Jiahui Wang, Na Zhou, Minsheng Zhu, Huaqun Chen

{"title":"TMEM16A regulates satellite cell-mediated skeletal muscle regeneration by ensuring a moderate level of caspase 3 activity.","authors":"Zhiyuan Sun, Xinqi Shan, Chun'e Fan, Lutao Liu, Shuai Li, Jiahui Wang, Na Zhou, Minsheng Zhu, Huaqun Chen","doi":"10.1093/stmcls/sxae048","DOIUrl":"10.1093/stmcls/sxae048","url":null,"abstract":"It has been documented that caspase 3 activity is necessary for skeletal muscle regeneration, but how its activity is regulated is largely unknown. Our previous report shows that intracellular TMEM16A, a calcium activated chloride channel, significantly regulates caspase 3 activity in myoblasts during skeletal muscle development. By using a mouse line with satellite cell (SC)-specific deletion of TMEM16A, we examined the role of TMEM16A in regulating caspase 3 activity in SC (or SC-derived myoblast) as well as skeletal muscle regeneration. The mutant animals displayed apparently impaired regeneration capacity in adult muscle along with enhanced ER stress and elevated caspase 3 activity in Tmem16a-/- SC derived myoblasts. Blockade of either excessive ER stress or caspase 3 activity by small molecules significantly restored the inhibited myogenic differentiation of Tmem16a-/- SCs, indicating that excessive caspase 3 activity resulted from TMEM16A deletion contributes to the impaired muscle regeneration and the upstream regulator of caspase 3 was ER stress. Our results revealed an essential role of TMEM16A in satellite cell-mediated skeletal muscle regeneration by ensuring a moderate level of caspase 3 activity.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"902-913"},"PeriodicalIF":4.0,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141887741","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

Metabolic conditioning enhances human bmMSC therapy of doxorubicin-induced heart failure. 新陈代谢调节增强了人类 bmMSC 对多柔比星诱发的心力衰竭的治疗效果。

IF 4 2区医学

STEM CELLS Pub Date : 2024-10-09 DOI: 10.1093/stmcls/sxae050

Virginie Jacques, Sabrina Benaouadi, Jean-Gerard Descamps, Nicolas Reina, Nicolas Espagnolle, Dimitri Marsal, Yannis Sainte-Marie, Alexandre Boudet, Carla Pinto, Thomas Farge, Frédérique Savagner

{"title":"Metabolic conditioning enhances human bmMSC therapy of doxorubicin-induced heart failure.","authors":"Virginie Jacques, Sabrina Benaouadi, Jean-Gerard Descamps, Nicolas Reina, Nicolas Espagnolle, Dimitri Marsal, Yannis Sainte-Marie, Alexandre Boudet, Carla Pinto, Thomas Farge, Frédérique Savagner","doi":"10.1093/stmcls/sxae050","DOIUrl":"10.1093/stmcls/sxae050","url":null,"abstract":"The therapeutic potential of bone marrow mesenchymal stromal cells (bmMSCs) to address heart failure needs improvement for better engraftment and survival. This study explores the role of metabolic sorting for human bmMSCs in coculture in vitro and on doxorubicin-induced heart failure mice models. Using functional, epigenetic, and gene expression approaches on cells sorted for mitochondrial membrane potential in terms of their metabolic status, we demonstrated that bmMSCs selected for their glycolytic metabolism presented proliferative advantage and resistance to oxidative stress thereby favoring cell engraftment. Therapeutic use of glycolytic bmMSCs rescued left ventricular ejection fraction and decreased fibrosis in mice models of acute heart failure. Metabolic changes were also related to epigenetic histone modifications such as lysine methylation. By targeting LSD1 (lysine-specific demethylase 1) as a conditioning agent to enhance the metabolic profile of bmMSCs, we deciphered the interplay between glycolysis and bmMSC functionality. Our study elucidates novel strategies for optimizing bmMSC-based treatments for heart failure, highlighting the metabolic properties of bmMSCs as a promising target for more effective cardiovascular regenerative therapies.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"874-888"},"PeriodicalIF":4.0,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141915670","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

Silencing endomucin in bone marrow sinusoids improves hematopoietic stem and progenitor cell homing during transplantation. 沉默骨髓窦中的内黏蛋白可改善移植过程中造血干细胞和祖细胞的归巢。

IF 4 2区医学

STEM CELLS Pub Date : 2024-10-09 DOI: 10.1093/stmcls/sxae046

Yue Li, Miao Ren, Hu Li, Zuo Zhang, Ke Yuan, Yujin Huang, Shengnan Yuan, Wen Ju, Yuan He, Kailin Xu, Lingyu Zeng

{"title":"Silencing endomucin in bone marrow sinusoids improves hematopoietic stem and progenitor cell homing during transplantation.","authors":"Yue Li, Miao Ren, Hu Li, Zuo Zhang, Ke Yuan, Yujin Huang, Shengnan Yuan, Wen Ju, Yuan He, Kailin Xu, Lingyu Zeng","doi":"10.1093/stmcls/sxae046","DOIUrl":"10.1093/stmcls/sxae046","url":null,"abstract":"Efficient homing of infused hematopoietic stem and progenitor cells (HSPCs) into the bone marrow (BM) is the prerequisite for successful hematopoietic stem cell transplantation. However, only a small part of infused HSPCs find their way to the BM niche. A better understanding of the mechanisms that facilitate HSPC homing will help to develop strategies to improve the initial HSPC engraftment and subsequent hematopoietic regeneration. Here, we show that irradiation upregulates the endomucin expression of endothelial cells in vivo and in vitro. Furthermore, depletion of endomucin in irradiated endothelial cells with short-interfering RNA (siRNA) increases the HSPC-endothelial cell adhesion in vitro. To abrogate the endomucin of BM sinusoidal endothelial cells (BM-SECs) in vivo, we develop a siRNA-loaded bovine serum albumin nanoparticle for targeted delivery. Nanoparticle-mediated siRNA delivery successfully silences endomucin expression in BM-SECs and improves HSPC homing during transplantation. These results reveal that endomucin plays a critical role in HSPC homing during transplantation and that gene-based manipulation of BM-SEC endomucin in vivo can be exploited to improve the efficacy of HSPC transplantation.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"889-901"},"PeriodicalIF":4.0,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141589138","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

Single-cell RNA sequencing reveals vascularization-associated cell subpopulations in dental pulp: PDGFRβ+ DPSCs with activated PI3K/AKT pathway. 单细胞 RNA 测序揭示了牙髓中与血管形成相关的细胞亚群：活化了 PI3K/AKT 通路的 PDGFRβ+ DPSCs。

IF 4 2区医学

STEM CELLS Pub Date : 2024-10-09 DOI: 10.1093/stmcls/sxae051

Tiankai Di, Liying Wang, Baixiang Cheng, Mingzhu Guo, Chao Feng, Zhenzhen Wu, Lulu Wang, Yujiang Chen

{"title":"Single-cell RNA sequencing reveals vascularization-associated cell subpopulations in dental pulp: PDGFRβ+ DPSCs with activated PI3K/AKT pathway.","authors":"Tiankai Di, Liying Wang, Baixiang Cheng, Mingzhu Guo, Chao Feng, Zhenzhen Wu, Lulu Wang, Yujiang Chen","doi":"10.1093/stmcls/sxae051","DOIUrl":"10.1093/stmcls/sxae051","url":null,"abstract":"Background: This study aims to address challenges in dental pulp regeneration therapy. The heterogeneity of DPSCs poses challenges, especially in stem cell transplantation for clinical use, particularly when sourced from donors of different ages and conditions.Methods: Pseudotime analysis was employed to analyze single-cell sequencing data, and immunohistochemical studies were conducted to investigate the expression of fibronectin 1 (FN1). We performed in vitro sorting of PDGFRβ+ DPSCs using flow cytometry. A series of functional assays, including cell proliferation, scratch, and tube formation assays, were performed to experimentally validate the vasculogenic capabilities of the identified PDGFRβ+ DPSC subset. Furthermore, gene-edited mouse models were utilized to demonstrate the importance of PDGFRβ+ DPSCs. Transcriptomic sequencing was conducted to compare the differences between PDGFRβ+ DPSCs and P1-DPSCs.Results: Single-cell sequencing analysis unveiled a distinct subset, PDGFRβ+ DPSCs, characterized by significantly elevated FN1 expression during dental pulp development. Subsequent cell experiments demonstrated that this subset possesses remarkable abilities to promote HUVEC proliferation, migration, and tube formation. Gene-edited mouse models confirmed the vital role of PDGFRβ+ DPSCs in dental pulp development. Transcriptomic sequencing and in vitro experiments demonstrated that the PDGFR/PI3K/AKT signaling pathway is a crucial factor mediating the proliferation rate and pro-angiogenic properties of PDGFRβ+ DPSCs.Conclusion: We defined a new subset, PDGFRβ+ DPSCs, characterized by strong proliferative activity and pro-angiogenic capabilities, demonstrating significant clinical translational potential.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"914-927"},"PeriodicalIF":4.0,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142015889","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

HGF Facilitates the Repair of Spinal Cord Injuries by Driving the Chemotactic Migration of MSCs Through the β-Catenin/TCF4/Nedd9 Signaling Pathway. HGF通过β-Catenin/TCF4/Nedd9信号通路驱动间充质干细胞的趋化迁移促进脊髓损伤的修复

IF 5.2 2区医学

STEM CELLS Pub Date : 2024-09-12 DOI: 10.1093/stmcls/sxae055

Ya'nan Hu,Huanhuan Chen,Min Yang,Jianwei Xu,Jinming Liu,Qisheng He,Xiaojing Xu,Zhongqing Ji,Ying Yang,Mengwen Yan,Huanxiang Zhang

{"title":"HGF Facilitates the Repair of Spinal Cord Injuries by Driving the Chemotactic Migration of MSCs Through the β-Catenin/TCF4/Nedd9 Signaling Pathway.","authors":"Ya'nan Hu,Huanhuan Chen,Min Yang,Jianwei Xu,Jinming Liu,Qisheng He,Xiaojing Xu,Zhongqing Ji,Ying Yang,Mengwen Yan,Huanxiang Zhang","doi":"10.1093/stmcls/sxae055","DOIUrl":"https://doi.org/10.1093/stmcls/sxae055","url":null,"abstract":"Transplanted mesenchymal stem cells (MSCs) can significantly aid in repairing spinal cord injuries (SCI) by migrating to and settling at the injury site. However, this process is typically inefficient, as only a small fraction of MSCs successfully reach the target lesion area. During SCI, the increased expression and secretion of hepatocyte growth factor (HGF) act as a chemoattractant that guides MSC migration. Nonetheless, the precise mechanisms by which HGF influences MSC migration are not fully understood. This study focused on unraveling the molecular pathways that drive MSC migration towards the SCI site in response to HGF. It was found that HGF can activate β-catenin signaling in MSCs either by phosphorylating LRP6 or by suppressing GSK3β phosphorylation through the AKT and ERK1/2 pathways, or by enhancing the expression and nuclear translocation of TCF4. This activation leads to elevated Nedd9 expression, which promotes focal adhesion formation and F-actin polymerization, facilitating chemotactic migration. Transplanting MSCs during peak HGF expression in injured tissues substantially improves nerve regeneration, reduces scarring, and enhances hind limb mobility. Additionally, prolonging HGF release can further boost MSC migration and engraftment, thereby amplifying regenerative outcomes. However, inhibiting HGF/Met or interfering with β-catenin or Nedd9 signaling significantly impairs MSC engraftment, obstructing tissue repair and functional recovery. Together, these findings provide a theoretical basis and practical strategy for MSC transplantation therapy in SCI, highlighting the specific molecular mechanisms by which HGF regulates β-catenin signaling in MSCs, ultimately triggering their chemotactic migration.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":"23 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142252548","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 mesenchymal stromal cells ameliorate cisplatin-induced acute and chronic kidney injury via TSG-6. 人间质基质细胞通过 TSG-6 改善顺铂诱导的急性和慢性肾损伤

IF 4 2区医学

STEM CELLS Pub Date : 2024-09-10 DOI: 10.1093/stmcls/sxae037

Ming Tang, Linguo Shen, Maozhi Tang, Ling Liu, Zhengsheng Rao, Zhilin Wang, Yadi Wang, Supei Yin, Shujing Li, Guilian Xu, Keqin Zhang

{"title":"Human mesenchymal stromal cells ameliorate cisplatin-induced acute and chronic kidney injury via TSG-6.","authors":"Ming Tang, Linguo Shen, Maozhi Tang, Ling Liu, Zhengsheng Rao, Zhilin Wang, Yadi Wang, Supei Yin, Shujing Li, Guilian Xu, Keqin Zhang","doi":"10.1093/stmcls/sxae037","DOIUrl":"10.1093/stmcls/sxae037","url":null,"abstract":"Cisplatin is widely used in tumor chemotherapy, but nephrotoxicity is an unavoidable side effect of cisplatin. Several studies have demonstrated that mesenchymal stromal cells (MSCs) ameliorate cisplatin-induced kidney injury, but the underlying mechanisms are unknown. In this study, the cisplatin-induced kidney injury mouse model was established by subjecting a single intraperitoneal injection with cisplatin. One hour before cisplatin injection, the mice received human bone marrow MSCs (hBM-MSCs) with or without siRNA-transfection, recombinant human tumor necrosis factor-α-stimulated gene/protein 6 (rhTSG-6), or PBS through the tail vein. In addition, cisplatin-stimulated HK-2 cells were treated with hBM-MSCs or rhTSG-6. Human BM-MSCs treatment remarkably ameliorated cisplatin-induced acute and chronic kidney injury, as evidenced by significant reductions in serum creatinine (Scr), blood urea nitrogen, tubular injury, collagen deposition, α-smooth muscle actin accumulation, as well as inflammatory responses, and by remarkable increased anti-inflammatory factor expression and Treg cells infiltration in renal tissues. Furthermore, we found that only a few hBM-MSCs engrafted into damaged kidney and that the level of human TSG-6 in the serum of mice increased significantly following hBM-MSCs administration. Moreover, hBM-MSCs significantly increased the viability of damaged HK-2 cells and decreased the levels of inflammatory cytokines in the culture supernatant. However, the knockdown of the TSG-6 gene in hBM-MSCs significantly attenuated their beneficial effects in vivo and in vitro. On the contrary, treated with rhTSG-6 achieved similar beneficial effects of hBM-MSCs. Our results indicate that systemic administration of hBM-MSCs alleviates cisplatin-induced acute and chronic kidney injury in part by paracrine TSG-6 secretion.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"848-859"},"PeriodicalIF":4.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141157261","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

Epigenetically rewiring metabolic genes via SIRT6 orchestrates MSC fate determination. 通过 SIRT6 对代谢基因进行表观遗传重编程可协调间充质干细胞命运的决定。

IF 4 2区医学

STEM CELLS Pub Date : 2024-09-10 DOI: 10.1093/stmcls/sxae041

Xueyang Liao, Feifei Li, Fanyuan Yu, Ling Ye

引用次数: 0

Advancing Parkinson's disease treatment: cell replacement therapy with neurons derived from pluripotent stem cells. 推进帕金森病治疗：多能干细胞衍生神经元的细胞替代疗法。

IF 4 2区医学

STEM CELLS Pub Date : 2024-09-10 DOI: 10.1093/stmcls/sxae042

Branden J Clark, Mariah J Lelos, Jeanne F Loring

{"title":"Advancing Parkinson's disease treatment: cell replacement therapy with neurons derived from pluripotent stem cells.","authors":"Branden J Clark, Mariah J Lelos, Jeanne F Loring","doi":"10.1093/stmcls/sxae042","DOIUrl":"10.1093/stmcls/sxae042","url":null,"abstract":"The motor symptoms of Parkinson's disease (PD) are caused by the progressive loss of dopamine neurons from the substantia nigra. There are currently no treatments that can slow or reverse the neurodegeneration. To restore the lost neurons, international groups have initiated clinical trials using human embryonic or induced pluripotent stem cells (PSCs) to derive dopamine neuron precursors that are used as transplants to replace the lost neurons. Proof-of-principle experiments in the 1980s and 1990s showed that grafts of fetal ventral mesencephalon, which contains the precursors of the substantial nigra, could, under rare circumstances, reverse symptoms of the disease. Improvements in PSC technology and genomics have inspired researchers to design clinical trials using PSC-derived dopamine neuron precursors as cell replacement therapy for PD. We focus here on 4 such first-in-human clinical trials that have begun in the US, Europe, and Japan. We provide an overview of the sources of PSCs and the methods used to generate cells for transplantation. We discuss pros and cons of strategies for allogeneic, immune-matched, and autologous approaches and novel methods for overcoming rejection by the immune system. We consider challenges for safety and efficacy of the cells for durable engraftment, focusing on the genomics-based quality control methods to assure that the cells will not become cancerous. Finally, since clinical trials like these have never been undertaken before, we comment on the value of cooperation among rivals to contribute to advancements that will finally provide relief for the millions suffering from the symptoms of PD.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"781-790"},"PeriodicalIF":4.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141430972","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