Our laboratory has been studying cell differentiation and regeneration of the cardiovascular system using embryonic stem (ES) and induced pluripotent stem (iPS) cells.
We have studied the differentiation of mesoderm-derived tissues: blood vessels and the heart, using ES cells. Vessel walls consist of 2 cell types: endothelial cell monolayer forming the lumen and mural cells surrounding the former, and blood cells flow in the lumen. A receptor for vascular endothelial cell growth factor (VEGF), Flk1, is considered to be a marker of the mesoderm. We selectively induced the differentiation of mesoderm and vascular cells (endothelial and mural cells) from ES cells, and achieved the reconstitution of a vascular structure in vitro, i.e., reproduction of the vascular developmental process (Yamashita, Nature, 2000). We also succeeded in inducing the differentiation of Flk1-positive cells into cardiomyocytes (Yamashita, FASEB J, 2005). The systemic induction of various cardiovascular cells from a common progenitor, Flk1-positive cells, has become possible. In addition, we applied our knowledge accumulated in the ES cell studies to mouse iPS cells recently established by Professor Shinya Yamanaka, and succeeded in inducing the differentiation of cardiovascular cells (Narazaki, Circulation, 2008). Using this differentiation system, we are proceeding with studies to investigate the cardiovascular development and differentiation mechanisms at the cell and molecular levels, and apply the data to regenerative medicine.