Pathway for differentiation of human embryonic stem cells to vascular cell components and their potential for vascular regeneration
Pathway for differentiation of human embryonic stem cells to vascular cell components and their potential for vascular regeneration
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DOI：
10.1161/atvbaha.107.143149
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发表时间：
2007-10-01
影响因子：
8.7
通讯作者：
Nakao, Kazuwa
中科院分区：
文献类型：
--
作者：
Sone, Masakatsu;Itoh, Hiroshi;Nakao, Kazuwa
我们以前证明小鼠胚胎干细胞来源的血管内皮生长因子受体2（VEGF-R2）阳性细胞可以分化为血管内皮细胞和壁细胞。这一次，我们研究了人ES细胞分化为血管细胞的动力学，并检查了它们作为血管再生源的潜力。方法和结果-与小鼠ES细胞不同，未分化的人ES细胞已经表达VEGF-R2，但分化后，出现了VEGF-R2阳性但肿瘤排斥抗原1-60（TRA 1 -60）阴性的群体。这些VEGF-R2阳性但肿瘤排斥抗原1-60阴性的细胞对血小板衍生生长因子受体α和β链也是阳性的，并且可以有效地分化为VE-钙粘蛋白（+）内皮细胞和α-平滑肌肌动蛋白（+）壁细胞。VE-cadherin（+）细胞，也是CD 34（+）和VEGF-R2（+），被认为是早期分化阶段的内皮细胞，可以在保持其成熟的同时扩增。他们的移植到后肢缺血模型的免疫缺陷小鼠的新血管的建设和改善bloodflow. Conclusions，我们可以确定从人ES细胞的分化过程中的血管细胞成分，并证明，血管细胞的扩张和移植在适当的分化阶段可能构成一种新的策略，血管再生医学。
Objective-We demonstrated previously that mouse embryonic stem (ES) cell-derived vascular endothelial growth factor receptor-2 (VEGF-R2)-positive cells can differentiate into both vascular endothelial cells and mural cells. This time, we investigated kinetics of differentiation of human ES cells to vascular cells and examined their potential as a source for vascular regeneration.Methods and Results-Unlike mouse ES cells, undifferentiated human ES cells already expressed VEGF-R2, but after differentiation, a VEGF- R2-positive but tumor rejection antigen 1-60 (TRA1-60)-negative population emerged. These VEGF- R2-positive but tumor rejection antigen 1-60-negative cells were also positive for platelet-derived growth factor receptor alpha and beta chains and could be effectively differentiated into both VE-cadherin(+) endothelial cell and alpha-smooth muscle actin(+) mural cell. VE-cadherin(+) cells, which were also CD34(+) and VEGF-R2(+) and thought to be endothelial cells in the early differentiation stage, could be expanded while maintaining their maturity. Their transplantation to the hindlimb ischemia model of immunodeficient mice contributed to the construction of new blood vessels and improved blood flow.Conclusions-We could identify the differentiation process from human ES cells to vascular cell components and demonstrate that expansion and transplantation of vascular cells at the appropriate differentiation stage may constitute a novel strategy for vascular regenerative medicine.