Augmentation of Neovascularizaiton in Hindlimb Ischemia by Combined Transplantation of Human Embryonic Stem Cells-Derived Endothelial and Mural Cells

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...

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Bibliographic Details
Published in:PloS one 2008-02, Vol.3 (2), p.e1666
Main Authors: Yamahara, Kenichi, Sone, Masakatsu, Itoh, Hiroshi, Yamashita, Jun K, Yurugi-Kobayashi, Takami, Homma, Koichiro, Chao, Ting-Hsing, Miyashita, Kazutoshi, Park, Kwijun, Oyamada, Naofumi, Sawada, Naoya, Taura, Daisuke, Fukunaga, Yasutomo, Tamura, Naohisa, Nakao, Kazuwa
Format: Article
Language:English
Subjects:
Augmentation
Blood
Blood flow
Blood vessels
Capillary flow
Cardiomyocytes
Cardiovascular Disorders/Vascular Biology
Cells (biology)
Collagen
Cord blood
Developmental Biology/Cell Differentiation
Developmental Biology/Stem Cells
Embryo cells
Embryonic stem cells
Endothelial cells
Endothelium
Health aspects
Hemopoiesis
Internal medicine
Ischemia
Kinases
Laboratories
Medical research
Medicine
Mice
Regeneration
Science
Smooth muscle
Stem cell transplantation
Stem cells
Transplantation
Umbilical cord
University graduates
Vascular endothelial growth factor
Vascular endothelial growth factor receptors
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0001666