Generation of Vascular Endothelial Cells and Hematopoietic Cells by Blastocyst Complementation

Publication date: Available online 20 September 2018Source: Stem Cell ReportsAuthor(s): Sanae Hamanaka, Ayumi Umino, Hideyuki Sato, Tomonari Hayama, Ayaka Yanagida, Naoaki Mizuno, Toshihiro Kobayashi, Mariko Kasai, Fabian Patrik Suchy, Satoshi Yamazaki, Hideki Masaki, Tomoyuki Yamaguchi, Hiromitsu NakauchiSummaryIn 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.Graphical Abstract
Source: Stem Cell Reports - Category: Stem Cells Source Type: research