Flk1-positive cells derived from embryonic stem cells serve as vascular progenitors

Jun Yamashita (), Hiroshi Itoh, Masanori Hirashima, Minetaro Ogawa, Satomi Nishikawa, Takami Yurugi, Makoto Naito, Kazuwa Nakao and Shin-Ichi Nishikawa
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Jun Yamashita: Department of Medicine and Clinical Science
Hiroshi Itoh: Department of Medicine and Clinical Science
Masanori Hirashima: Kyoto University Graduate School of Medicine
Minetaro Ogawa: Kyoto University Graduate School of Medicine
Satomi Nishikawa: Kyoto University Graduate School of Medicine
Takami Yurugi: Department of Medicine and Clinical Science
Makoto Naito: The Second Department of Pathology Niigata Univeristy School of Medicine
Kazuwa Nakao: Department of Medicine and Clinical Science
Shin-Ichi Nishikawa: Kyoto University Graduate School of Medicine

Nature, 2000, vol. 408, issue 6808, 92-96

Abstract: Abstract Interaction between endothelial cells and mural cells (pericytes and vascular smooth muscle) is essential for vascular development and maintenance1,2,3,4. Endothelial cells arise from Flk1-expressing (Flk1+) mesoderm cells5, whereas mural cells are believed to derive from mesoderm, neural crest or epicardial cells and migrate to form the vessel wall6,7,8. Difficulty in preparing pure populations of these lineages has hampered dissection of the mechanisms underlying vascular formation. Here we show that Flk1+ cells derived from embryonic stem cells can differentiate into both endothelial and mural cells and can reproduce the vascular organization process. Vascular endothelial growth factor promotes endothelial cell differentiation, whereas mural cells are induced by platelet-derived growth factor-BB. Vascular cells derived from Flk1+ cells can organize into vessel-like structures consisting of endothelial tubes supported by mural cells in three-dimensional culture. Injection of Flk1+ cells into chick embryos showed that they can incorporate as endothelial and mural cells and contribute to the developing vasculature in vivo. Our findings indicate that Flk1+ cells can act as ‘vascular progenitor cells’ to form mature vessels and thus offer potential for tissue engineering of the vascular system.

Date: 2000
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DOI: 10.1038/35040568

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