RRC ID 2437
Author Sone M, Itoh H, Yamahara K, Yamashita JK, Yurugi-Kobayashi T, Nonoguchi A, Suzuki Y, Chao TH, Sawada N, Fukunaga Y, Miyashita K, Park K, Oyamada N, Sawada N, Taura D, Tamura N, Kondo Y, Nito S, Suemori H, Nakatsuji N, Nishikawa S, Nakao K.
Title Pathway for differentiation of human embryonic stem cells to vascular cell components and their potential for vascular regeneration.
Journal Arterioscler. Thromb. Vasc. Biol.
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 alpha and beta chains and could be effectively differentiated into both VE-cadherin+ endothelial cell and alpha-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.
Volume 27(10)
Pages 2127-34
Published 2007-10
DOI 10.1161/ATVBAHA.107.143149
PII ATVBAHA.107.143149
PMID 17872458
MeSH Actins / metabolism Angiogenic Proteins / metabolism Animals Antigens, CD / metabolism Antigens, Neoplasm / metabolism Cadherins / metabolism Cell Differentiation* Cell Line Cell Proliferation* Cell Transformation, Neoplastic / metabolism Disease Models, Animal Embryonic Stem Cells / immunology Embryonic Stem Cells / metabolism* Endothelial Cells / immunology Endothelial Cells / metabolism* Endothelial Cells / transplantation Hindlimb / blood supply Humans Ischemia / metabolism Ischemia / physiopathology Ischemia / surgery Kinetics Mice Mice, Inbred C57BL Mice, Nude Myocytes, Smooth Muscle / immunology Myocytes, Smooth Muscle / metabolism* Myocytes, Smooth Muscle / transplantation Neovascularization, Physiologic Receptor, Platelet-Derived Growth Factor alpha / metabolism Receptor, Platelet-Derived Growth Factor beta / metabolism Regeneration* Regional Blood Flow Stem Cell Transplantation Vascular Endothelial Growth Factor Receptor-2 / metabolism
IF 6.618
Times Cited 108
Human embryonic stem cells KhES-1