Augmentation of neovascularization [corrected] in hindlimb ischemia by combined transplantation of human embryonic stem cells-derived endothelial and mural cells.
Augmentation of neovascularization [corrected] in hindlimb ischemia by combined transplantation of human embryonic stem cells-derived endothelial and mural cells.
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DOI：
10.1371/journal.pone.0001666
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发表时间：
2008-02-27
期刊：
影响因子：
3.7
通讯作者：
Nakao K
中科院分区：
文献类型：
--
作者：
Yamahara K;Sone M;Itoh H;Yamashita JK;Yurugi-Kobayashi T;Homma K;Chao TH;Miyashita K;Park K;Oyamada N;Sawada N;Taura D;Fukunaga Y;Tamura N;Nakao K
本实验证明小鼠胚胎干细胞（ES细胞）来源的血管内皮生长因子受体2（VEGF-R2）阳性细胞可分化为内皮细胞（EC）和壁细胞（MC），称之为血管祖细胞（VPC）。最近，我们已经建立了一种方法来大量扩增具有适当分化阶段的猴和人ES细胞来源的VPC。在这里，我们研究了人VPC衍生的EC和MC用于血管再生的治疗潜力。在扩增人VPC衍生的血管细胞后，我们将这些细胞移植到后肢缺血的裸鼠体内。与人外周血和脐带血来源的内皮祖细胞（pEPC和uEPC）移植小鼠相比，人VPC来源的EC移植小鼠缺血后肢的血流恢复和毛细血管密度显着改善。与单细胞移植相比，人VPC来源的EC和MC联合移植显著改善了缺血后肢的血流量。移植的VPC衍生的血管细胞有效地并入宿主循环血管作为EC和MC以维持长期的血管完整性。我们的研究结果表明，联合移植人ES细胞来源的EC和MC可以作为一个新的有前途的策略，治疗组织缺血患者的血管再生。
We demonstrated that mouse embryonic stem (ES) cells-derived vascular endothelial growth factor receptor-2 (VEGF-R2) positive cells could differentiate into both endothelial cells (EC) and mural cells (MC), and termed them as vascular progenitor cells (VPC). Recently, we have established a method to expand monkey and human ES cells-derived VPC with the proper differentiation stage in a large quantity. Here we investigated the therapeutic potential of human VPC-derived EC and MC for vascular regeneration. After the expansion of human VPC-derived vascular cells, we transplanted these cells to nude mice with hindlimb ischemia. The blood flow recovery and capillary density in ischemic hindlimbs were significantly improved in human VPC-derived EC-transplanted mice, compared to human peripheral and umbilical cord blood-derived endothelial progenitor cells (pEPC and uEPC) transplanted mice. The combined transplantation of human VPC-derived EC and MC synergistically improved blood flow of ischemic hindlimbs remarkably, compared to the single cell transplantations. Transplanted VPC-derived vascular cells were effectively incorporated into host circulating vessels as EC and MC to maintain long-term vascular integrity. Our findings suggest that the combined transplantation of human ES cells-derived EC and MC can be used as a new promising strategy for therapeutic vascular regeneration in patients with tissue ischemia.
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影响因子：
56.9
作者：
Asahara, T;Murohara, T;Isner, JM
通讯作者：
Isner, JM
影响因子：
37.8
作者：
Sone, M;Itoh, H;Nakao, K
通讯作者：
Nakao, K
DOI：
10.1016/j.bbrc.2003.08.134
发表时间：
2003-10-10
影响因子：
3.1
作者：
Fukino, K;Sata, M;Nagai, R
通讯作者：
Nagai, R
影响因子：
5.5
作者：
Xiao, Qingzhong;Zeng, Lingfang;Xu, Qingbo
通讯作者：
Xu, Qingbo
影响因子：
15.9
作者：
Kehat, I;Kenyagin-Karsenti, D;Gepstein, L
通讯作者：
Gepstein, L