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Letters to Nature

Nature 408, 92-96 (2 November 2000) | doi:10.1038/35040568; Received 26 June 2000; Accepted 23 August 2000

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

Jun Yamashita1, Hiroshi Itoh1, Masanori Hirashima2, Minetaro Ogawa2, Satomi Nishikawa2, Takami Yurugi1, Makoto Naito3, Kazuwa Nakao1 & Shin-Ichi Nishikawa2

  1. Department of Medicine and Clinical Science, and
  2. Department of Molecular Genetics, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8509, Japan
  3. The Second Department of Pathology, Niigata Univeristy School of Medicine, Asahimachi-dori 1, Niigata 951-8510, Japan

Correspondence to: Jun Yamashita1 Correspondence and requests for materials should be addressed to J.Y. (e-mail: Email: juny@kuhp.kyoto-u.ac.jp).

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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.

  1. Department of Medicine and Clinical Science, and
  2. Department of Molecular Genetics, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8509, Japan
  3. The Second Department of Pathology, Niigata Univeristy School of Medicine, Asahimachi-dori 1, Niigata 951-8510, Japan

Correspondence to: Jun Yamashita1 Correspondence and requests for materials should be addressed to J.Y. (e-mail: Email: juny@kuhp.kyoto-u.ac.jp).