title: Generation of robust vascular networks from cardiovascular blast populations derived from human induced pluripotent stem cells in vivo and ex vivo organ culture system.
abstract: Vascular network formation is a key therapeutic event in regenerative medicine because it is essential for mitigating or ameliorating ischemic conditions implicated in various diseases and repair of tissues and organs. In this study, we induced human induced pluripotent stem cells (hiPSCs) to differentiate into heterogeneous cell populations which have abilities to form vascular vessel-like structures by recapitulating the embryonic process of vasculogenesis in vitro. These cell populations, named cardiovascular blast populations (CBPs) in this report, primarily consisted of CD31(+) and CD90(+) cells. By using cell-sheet technology, we observed that CBP with CD31(+) cells to CD90(+) cells in the ratio of 1:1.5 could reproducibly form robust vascular networks in vivo and ex vivo organ culture system. To our knowledge, this is the first report demonstrating the generation of vascular network from hiPSCs in ex vivo organ culture system that correlates closely with in vivo results. Our results suggest that CBP provides a promising approach for studying vasculogenesis and subsequently can be used in regenerative medicine.
authors.affiliation: Molecular Medicine Research Laboratories, Drug Discovery Research, Astellas Pharma Inc., Tsukuba, Ibaraki, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kawamoto
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Hidenori
authors.initials: H
authors.lastname: Nakajima
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Yamagishi
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000254:growth & development*; D002469:Cell Separation; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D008297:Male; D051379:Mice; D016513:Mice, SCID; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000637:transplantation; D018919:Neovascularization, Physiologic; D009924:Organ Culture Techniques / Q000379:methods*; D010477:Perfusion; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D018800:Thy-1 Antigens / Q000378:metabolism
chemical_list: D019408:Platelet Endothelial Cell Adhesion Molecule-1; D018800:Thy-1 Antigens
keywords: Ex vivo organ culture system; Human induced pluripotent stem cells; Vascular vessel