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- Title
Augmentation of Neovascularizaiton in Hindlimb Ischemia by Combined Transplantation of Human Embryonic Stem Cells-Derived Endothelial and Mural Cells.
- Authors
Yamahara, Kenichi; Sone, Masakatsu; Itoh, Hiroshi; Yamashita, Jun K.; Yurugi-Kobayashi, Takami; Homma, Koichiro; Ting-Hsing Chao; Miyashita, Kazutoshi; Kwijun Park; Oyamada, Naofumi; Sawada, Naoya; Taura, Daisuke; Fukunaga, Yasutomo; Tamura, Naohisa; Nakao, Kazuwa
- 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.
- Subjects
EMBRYONIC stem cells; VASCULAR endothelial growth factors; ENDOTHELIAL seeding; ISCHEMIA; BLOOD flow; BLOOD circulation; HYBRID embryos; STEM cells; GROWTH factors
- Publication
PLoS ONE, 2008, Vol 3, Issue 2, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0001666