Pathway for differentiation of human embryonic stem cells to vascular cell components and their potential for vascular regeneration

Masakatsu Sone, Hiroshi Itoh, Kenichi Yamahara, Jun K. Yamashita, Takami Yurugi-Kobayashi, Akane Nonoguchi, Yutaka Suzuki, Ting Hsing Chao, Naoki Sawada, Yasutomo Fukunaga, Kazutoshi Miyashita, Kwijun Park, Naofumi Oyamada, Naoya Sawada, Daisuke Taura, Naohisa Tamura, Yasushi Kondo, Shinji Nito, Hirofumi Suemori, Norio NakatsujiShin Ichi Nishikawa, Kazuwa Nakao

Research output: Contribution to journalArticle

121 Citations (Scopus)

Abstract

OBJECTIVE - We demonstrated previously that mouse embryonic stem (ES) cell-derived vascular endothelial growth factor receptor-2 (VEGF-R2)-positive cells can differentiate into both vascular endothelial cells and mural cells. This time, we investigated kinetics of differentiation of human ES cells to vascular cells and examined their potential as a source for vascular regeneration. METHODS AND RESULTS - Unlike mouse ES cells, undifferentiated human ES cells already expressed VEGF-R2, but after differentiation, a VEGF-R2-positive but tumor rejection antigen 1-60 (TRA1-60)-negative population emerged. These VEGF-R2-positive but tumor rejection antigen 1-60-negative cells were also positive for platelet-derived growth factor receptor α and β chains and could be effectively differentiated into both VE-cadherin endothelial cell and α-smooth muscle actin mural cell. VE-cadherin cells, which were also CD34 and VEGF-R2 and thought to be endothelial cells in the early differentiation stage, could be expanded while maintaining their maturity. Their transplantation to the hindlimb ischemia model of immunodeficient mice contributed to the construction of new blood vessels and improved blood flow. CONCLUSIONS - We could identify the differentiation process from human ES cells to vascular cell components and demonstrate that expansion and transplantation of vascular cells at the appropriate differentiation stage may constitute a novel strategy for vascular regenerative medicine.

Original languageEnglish
Pages (from-to)2127-2134
Number of pages8
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume27
Issue number10
DOIs
Publication statusPublished - 2007 Oct 1

Keywords

  • Angiogenesis
  • Developmental biology
  • Embryonic stem cells
  • Endothelium
  • Vascular biology

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Sone, M., Itoh, H., Yamahara, K., Yamashita, J. K., Yurugi-Kobayashi, T., Nonoguchi, A., Suzuki, Y., Chao, T. H., Sawada, N., Fukunaga, Y., Miyashita, K., Park, K., Oyamada, N., Sawada, N., Taura, D., Tamura, N., Kondo, Y., Nito, S., Suemori, H., ... Nakao, K. (2007). Pathway for differentiation of human embryonic stem cells to vascular cell components and their potential for vascular regeneration. Arteriosclerosis, Thrombosis, and Vascular Biology, 27(10), 2127-2134. https://doi.org/10.1161/ATVBAHA.107.143149