Multipotent Vasculogenic Pericytes From Human Pluripotent Stem Cells Promote Recovery of Murine Ischemic Limb
Multipotent Vasculogenic Pericytes From Human Pluripotent Stem Cells Promote Recovery of Murine Ischemic Limb
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DOI：
10.1161/circulationaha.111.048264
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发表时间：
2012-01-03
期刊：
影响因子：
37.8
通讯作者：
Itskovitz-Eldor, Joseph
中科院分区：
文献类型：
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作者：
Dar, Ayelet;Domev, Hagit;Itskovitz-Eldor, Joseph
周细胞是一种独特的微血管周围细胞亚型，具有多种血管生成功能和间充质干细胞的多谱系发育特征。虽然已经描述了从人多能干细胞（hPSC，胚胎或诱导）衍生内皮细胞和/或平滑肌细胞的各种方案，但在hPSC成熟过程中周细胞的出现尚未阐明。方法与结果-我们发现在hPSC发育过程中，自发分化的胚样体可产生CD105(+)CD90(+)CD73(+)CD31（-）多能克隆源性中胚层前体，该前体可被分离并有效扩增。分离和繁殖的细胞表达特征性的周细胞标记物，包括CD146、NG2和血小板衍生的生长因子受体β，但不表达平滑肌细胞标记物α -平滑肌肌动蛋白。hpsc来源的内皮细胞与周细胞共植入可实现与小鼠血管的功能性快速吻合。将周细胞注入肢体缺血免疫缺陷小鼠体内，可显著促进血管和肌肉再生。移植后第21天，招募的hPSC周细胞被纳入恢复的肌肉和血管系统。结论：从hPSC中衍生血管生成和多能性周细胞可用于多种血管生成细胞类型的血管生成模型的建立，用于基础研究和药物筛选，对血管生成再生医学有重要意义。(循环。2012;125:87 - 99)。
Background-Pericytes represent a unique subtype of microvessel-residing perivascular cells with diverse angiogenic functions and multilineage developmental features of mesenchymal stem cells. Although various protocols for derivation of endothelial and/or smooth muscle cells from human pluripotent stem cells (hPSC, either embryonic or induced) have been described, the emergence of pericytes in the course of hPSC maturation has not yet been elucidated.Methods and Results-We found that during hPSC development, spontaneously differentiating embryoid bodies give rise to CD105(+)CD90(+)CD73(+)CD31(-) multipotent clonogenic mesodermal precursors, which can be isolated and efficiently expanded. Isolated and propagated cells expressed characteristic pericytic markers, including CD146, NG2, and platelet-derived growth factor receptor beta, but not the smooth muscle cell marker alpha-smooth muscle actin. Coimplantation of hPSC-derived endothelial cells with pericytes resulted in functional and rapid anastomosis to the murine vasculature. Administration of pericytes into immunodeficient mice with limb ischemia promoted significant vascular and muscle regeneration. At day 21 after transplantation, recruited hPSC pericytes were found incorporated into recovered muscle and vasculature.Conclusions-Derivation of vasculogenic and multipotent pericytes from hPSC can be used for the development of vasculogenic models using multiple vasculogenic cell types for basic research and drug screening and can contribute to angiogenic regenerative medicine. (Circulation. 2012;125:87-99.)