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Augmentation of Neovascularizaiton in Hindlimb Ischemia by Combined Transplantation of Human Embryonic Stem Cells-Derived Endothelial and Mural Cells
Authors:Kenichi Yamahara  Masakatsu Sone  Hiroshi Itoh  Jun K Yamashita  Takami Yurugi-Kobayashi  Koichiro Homma  Ting-Hsing Chao  Kazutoshi Miyashita  Kwijun Park  Naofumi Oyamada  Naoya Sawada  Daisuke Taura  Yasutomo Fukunaga  Naohisa Tamura  Kazuwa Nakao
Institution:1. Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, Japan.; 2. Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.; 3. Laboratory of Stem Cell Differentiation, Stem Cell Research Center, Institute for Frontier Medical Science, Kyoto University, Kyoto, Japan.; 4. Division of Cardiology, Department of Internal Medicine, National Cheng Kung University Medical Center, Tainan, Taiwan.;University of Sydney, Australia
Abstract:

Background

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.

Methods and Results

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.

Conclusions

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.
Keywords:
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