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源自骨髓间充质干细胞的CXCR4+祖细胞可分化为动脉损伤后具有血管修复能力的内皮细胞。

CXCR4+ progenitors derived from bone mesenchymal stem cells differentiate into endothelial cells capable of vascular repair after arterial injury.

作者信息

Li Mincai, Yu Jun, Li Yan, Li Dujuan, Yan Dan, Ruan Qiurong

机构信息

Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.

出版信息

Cell Reprogram. 2010 Aug;12(4):405-15. doi: 10.1089/cell.2009.0088.

Abstract

Recent findings indicate that bone marrow mesenchymal stem cells (BMSCs) participate in the process of neovascularization in response to repair to injury and are involved in postinfarction myocardial repair. It is unclear what special characteristics the vascular progenitors of bone marrow origin has. CXCR4(+) stem/progenitor cells mobilized to the infarct area and improved the myocardial repair. In present study, we aimed to determine whether CXCR4(+)BMSCs contribute to the angiogenic capacity in vitro and in vivo. CXCR4(+)BMSCs were separated by using paramagnetic microbeads and cultured. RT-PCR and FACS analysis confirmed the gene expression phenotype. The uptake of acetylated low density lipoprotein (acLDL) and the tube formation evaluated the function of CXCR4(+)BMSCs. The effect of CXCR4(+)BMSCs transplantation on neovascularization was investigated in a murine model hindlimb ischemia. After induced by VEGF, CXCR4(+)BMSCs expressed the endothelial cells (ECs) phenotype. The expression of EC markers, PECAM-1, and von Willebrand factor (vWF) increased significantly at both the mRNA and protein levels. In addition, CXCR4(+)BMSCs enhanced the uptakes of Dil-acLDL and form capillary-like tubes in vitro. In vivo the local transfer of CXCR4(+)BMSCs increased neovascularization in ischemic hindlimb. These results demonstrate that CXCR4(+)BMSCs differentiate into ECs and contribute to neovascularization in the vascular lesion,, which indicate the important therapeutic implications for cardiovascular diseases and a new cell source for cell-based vascular engineering and repair in the future.

摘要

最近的研究结果表明,骨髓间充质干细胞(BMSCs)参与损伤修复过程中的新血管形成,并参与心肌梗死后的心肌修复。目前尚不清楚骨髓来源的血管祖细胞有哪些特殊特征。动员至梗死区域的CXCR4(+)干/祖细胞可改善心肌修复。在本研究中,我们旨在确定CXCR4(+)BMSCs在体外和体内是否具有血管生成能力。通过使用顺磁性微珠分离并培养CXCR4(+)BMSCs。RT-PCR和FACS分析证实了基因表达表型。通过乙酰化低密度脂蛋白(acLDL)摄取和管形成评估CXCR4(+)BMSCs的功能。在小鼠后肢缺血模型中研究了CXCR4(+)BMSCs移植对新血管形成的影响。在VEGF诱导后,CXCR4(+)BMSCs表达内皮细胞(ECs)表型。EC标志物PECAM-1和血管性血友病因子(vWF)在mRNA和蛋白质水平上的表达均显著增加。此外,CXCR4(+)BMSCs在体外增强了Dil-acLDL的摄取并形成毛细血管样管。在体内,CXCR4(+)BMSCs的局部转移增加了缺血后肢的新血管形成。这些结果表明,CXCR4(+)BMSCs可分化为ECs并促进血管病变中的新血管形成,这对心血管疾病具有重要的治疗意义,并为未来基于细胞的血管工程和修复提供了一种新的细胞来源。

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