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 Honma, Ting Hsing Chao, Kazutoshi Miyashita, Kwijun Park, Naofumi Oyamada, Naoya Sawada, Daisuke Taura, Yasutomo Fukunaga, Naohisa Tamura, Kazuwa Nakao

Research output: Contribution to journalArticle

85 Citations (Scopus)

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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Endothelial cells
embryonic stem cells
Hindlimb
ischemia
angiogenesis
Stem cells
blood vessels
Blood Vessels
Ischemia
Endothelial Cells
Transplantation
stem cells
endothelial cells
Stem Cells
cells
Blood
mice
Vascular Endothelial Growth Factor Receptor-2
blood flow
hindlimbs

ASJC Scopus subject areas

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

Cite this

Augmentation of neovascularization in hindlimb ischemia by combined transplantation of human embryonic stem cells-derived endothelial and mural cells. / Yamahara, Kenichi; Sone, Masakatsu; Itoh, Hiroshi; Yamashita, Jun K.; Yurugi-Kobayashi, Takami; Honma, Koichiro; Chao, Ting Hsing; Miyashita, Kazutoshi; Park, Kwijun; Oyamada, Naofumi; Sawada, Naoya; Taura, Daisuke; Fukunaga, Yasutomo; Tamura, Naohisa; Nakao, Kazuwa.

In: PLoS One, Vol. 3, No. 2, e1666, 27.02.2008.

Research output: Contribution to journalArticle

Yamahara, K, Sone, M, Itoh, H, Yamashita, JK, Yurugi-Kobayashi, T, Honma, K, Chao, TH, 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, vol. 3, no. 2, e1666. https://doi.org/10.1371/journal.pone.0001666
Yamahara, Kenichi ; Sone, Masakatsu ; Itoh, Hiroshi ; Yamashita, Jun K. ; Yurugi-Kobayashi, Takami ; Honma, Koichiro ; Chao, Ting Hsing ; Miyashita, Kazutoshi ; Park, Kwijun ; Oyamada, Naofumi ; Sawada, Naoya ; Taura, Daisuke ; Fukunaga, Yasutomo ; Tamura, Naohisa ; Nakao, Kazuwa. / Augmentation of neovascularization in hindlimb ischemia by combined transplantation of human embryonic stem cells-derived endothelial and mural cells. In: PLoS One. 2008 ; Vol. 3, No. 2.
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AU - Sone, Masakatsu

AU - Itoh, Hiroshi

AU - Yamashita, Jun K.

AU - Yurugi-Kobayashi, Takami

AU - Honma, Koichiro

AU - Chao, Ting Hsing

AU - Miyashita, Kazutoshi

AU - Park, Kwijun

AU - Oyamada, Naofumi

AU - Sawada, Naoya

AU - Taura, Daisuke

AU - Fukunaga, Yasutomo

AU - Tamura, Naohisa

AU - Nakao, Kazuwa

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