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Generation of Vascular Endothelial Cells and Hematopoietic Cells by Blastocyst Complementation.

Published version
Peer-reviewed

Type

Article

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Authors

Hamanaka, Sanae 
Umino, Ayumi 
Sato, Hideyuki 
Hayama, Tomonari 

Abstract

In the case of organ transplantation accompanied by vascular anastomosis, major histocompatibility complex mismatched vascular endothelial cells become a target for graft rejection. Production of a rejection-free, transplantable organ, therefore, requires simultaneous generation of vascular endothelial cells within the organ. To generate pluripotent stem cell (PSC)-derived vascular endothelial cells, we performed blastocyst complementation with a vascular endothelial growth factor receptor-2 homozygous mutant blastocyst. This mutation is embryonic lethal at embryonic (E) day 8.5-9.5 due to an early defect in endothelial and hematopoietic cells. The Flk-1 homozygous knockout chimeric mice survived to adulthood for over 1 year without any abnormality, and all vascular endothelial cells and hematopoietic cells were derived from the injected PSCs. This approach could be used in conjunction with other gene knockouts which induce organ deficiency to produce a rejection-free, transplantable organ in which all the organ's cells and vasculature are PSC derived.

Description

Keywords

blastocyst complementation, hematopoietic cells, pluripotent stem cells, tissue regeneration, vascular endothelial cells, Aging, Animals, Blastocyst, Chimera, Endothelial Cells, Hematopoietic Stem Cells, Induced Pluripotent Stem Cells, Mice, Inbred C57BL, Mice, Knockout, Neovascularization, Physiologic, Pericytes, Phenotype, Platelet Endothelial Cell Adhesion Molecule-1, Vascular Endothelial Growth Factor Receptor-2

Journal Title

Stem Cell Reports

Conference Name

Journal ISSN

2213-6711
2213-6711

Volume Title

11

Publisher

Elsevier BV