Augmentation of neovascularization in hindlimb ischemia by combined transplantation of human embryonic stem cells-derived endothelial and mural cells

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

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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.

Original languageEnglish
Article numbere1666
JournalPloS one
Volume3
Issue number2
DOIs
Publication statusPublished - 2008 Feb 27

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Yamahara, K., Sone, M., Itoh, H., Yamashita, J. K., Yurugi-Kobayashi, T., Homma, K., Chao, T. H., Miyashita, K., Park, K., Oyamada, N., Sawada, N., Taura, D., Fukunaga, Y., Tamura, N., & Nakao, K. (2008). Augmentation of neovascularization in hindlimb ischemia by combined transplantation of human embryonic stem cells-derived endothelial and mural cells. PloS one, 3(2), [e1666]. https://doi.org/10.1371/journal.pone.0001666