STEM CELLS最新文献_第3页

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

Correction to: Combination of Systemic Chemotherapy with Local Stem Cell Delivered S-TRAIL in Resected Brain Tumors. 更正：全身化疗与局部干细胞给药 S-TRAIL 在切除脑肿瘤中的联合应用。

IF 4 2区医学

STEM CELLS Pub Date : 2024-10-07 DOI: 10.1093/stmcls/sxae059

引用次数: 0

Enforced HCELL Expression Enhances Bone Marrow Stromal Cells Homing and Amelioration of Cerebral Ischemia-Reperfusion Injury via induction of PGE2. 强制 HCELL 表达可通过诱导 PGE2 增强骨髓基质细胞的归巢并改善脑缺血再灌注损伤。

IF 4 2区医学

STEM CELLS Pub Date : 2024-10-04 DOI: 10.1093/stmcls/sxae062

Lian Yi, Yewei Qu, Qi Zhang, Shanshan Shi, Fangqin Li, Changda Qu, Yushi Tang, Shirong Wen, Yujun Pan

{"title":"Enforced HCELL Expression Enhances Bone Marrow Stromal Cells Homing and Amelioration of Cerebral Ischemia-Reperfusion Injury via induction of PGE2.","authors":"Lian Yi, Yewei Qu, Qi Zhang, Shanshan Shi, Fangqin Li, Changda Qu, Yushi Tang, Shirong Wen, Yujun Pan","doi":"10.1093/stmcls/sxae062","DOIUrl":"10.1093/stmcls/sxae062","url":null,"abstract":"Ischemic stroke (IS) is a significant and potentially life-threatening disease with limited treatment options, often resulting in severe disability. Bone marrow stromal cells (BMSCs) transplantation has exhibited promising neuroprotection following cerebral ischemia-reperfusion injury (CIRI). However, the effectiveness is hindered by their low homing rate when administered through the vein. In this study, we aimed to enhance the homing ability of BMSCs through lentivirus transfection to express fucosyltransferase 7. This glycosylation engineered CD44 on BMSCs to express hematopoietic cell E-selectin/L-selectin ligand (HCELL), which is the most potent E-selectin ligand. Following enforced HCELL expression, the transplantation of BMSCs was then evaluated in a middle cerebral artery occlusion (MCAO) model. Results showed that HCELL+BMSCs significantly ameliorated neurological deficits and reduced the volume of cerebral infarction. Furthermore, the transplantation led to a decrease in apoptosis by up-regulating BCL-2 and down-regulating BAX, also reduced the mRNA levels of inflammatory factors, such as interleukin-1β (IL-1β), IL-2, IL-6 and tumor necrosis factor-alpha (TNF-α) in the ischemic brain tissue. Notably, enforced HCELL expression facilitated the migration of BMSCs towards cerebral ischemic lesions and their subsequent transendothelial migration through the up-regulation of PTGS-2, increased production of PGE2 and activation of VLA-4. In summary, our study demonstrates that transplantation of HCELL+BMSCs effectively alleviates CIRI, and that enforced HCELL expression enhances the homing of BMSCs to cerebral ischemic lesions and their transendothelial migration via PTGS-2/PGE2/VLA-4. These findings indicate that enforced expression of HCELL on BMSCs could serve as a promising therapeutic strategy for the treatment of ischemic stroke.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142370460","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

CD44: A Stemness Driver, Regulator and Marker - all in one? CD44：集干性驱动因子、调节因子和标记因子于一身？

IF 4 2区医学

STEM CELLS Pub Date : 2024-10-04 DOI: 10.1093/stmcls/sxae060

Steffen J Sonnentag, Nagwa S M Ibrahim, Veronique Orian-Rousseau

引用次数: 0

Metformin acts on miR-181a-5p/PAI-1 axis in stem cells providing new strategies for improving age-related osteogenic differentiation decline. 二甲双胍作用于干细胞中的 miR-181a-5p/PAI-1 轴，为改善与年龄相关的成骨分化衰退提供了新策略。

IF 4 2区医学

STEM CELLS Pub Date : 2024-09-16 DOI: 10.1093/stmcls/sxae057

Guanhao Hong, Yulan Zhou, Shukai Yang, Shouquan Yan, Jiaxu Lu, Bo Xu, Zeyu Zhan, Huasheng Jiang, Bo Wei, Jiafeng Wang

{"title":"Metformin acts on miR-181a-5p/PAI-1 axis in stem cells providing new strategies for improving age-related osteogenic differentiation decline.","authors":"Guanhao Hong, Yulan Zhou, Shukai Yang, Shouquan Yan, Jiaxu Lu, Bo Xu, Zeyu Zhan, Huasheng Jiang, Bo Wei, Jiafeng Wang","doi":"10.1093/stmcls/sxae057","DOIUrl":"https://doi.org/10.1093/stmcls/sxae057","url":null,"abstract":"A general decline in the osteogenic differentiation capacity of human bone marrow mesenchymal stem cells (hBMSCs) in the elderly is a clinical consensus, with diverse opinions on the mechanisms. Many studies have demonstrated that metformin (MF) significantly protects against osteoporosis and reduces fracture risk. However, the exact mechanism of this effect remains unclear. In this study, we found that the decreased miR-181a-5p expression triggered by MF treatment plays a critical role in recovering the osteogenic ability of aging hBMSCs (derived from elderly individuals). Notably, the miR-181a-5p expression in hBMSCs was significantly decreased with prolonged MF (1000 μM) treatment. Further investigation revealed that miR-181a-5p overexpression markedly impairs the osteogenic ability of hBMSCs, while miR-181a-5p inhibition reveals the opposite result. We also found that miR-181a-5p could suppress the protein translation process of plasminogen activator inhibitor-1 (PAI-1), as evidenced by luciferase assays and western blots. Additionally, low PAI-1 levels were associated with diminished osteogenic ability, whereas high levels promoted it. These findings were further validated in human umbilical cord mesenchymal stem cells (hUCMSCs). Finally, our in vivo experiment with a bone defects rat model confirmed that the agomiR-181a-5p (long-lasting miR-181a-5p mimic) undermined bone defects recovery, while the antagomiR-181a-5p (long-lasting miR-181a-5p inhibitor) significantly promoted the bone defects recovery. In conclusion, we found that MF promotes bone tissue regeneration through the miR-181a-5p/PAI-1 axis by affecting MSC osteogenic ability, providing new strategies for the treatment of age-related bone regeneration disorders.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142277717","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