Generation of Vascular Endothelial Cells and Hematopoietic Cells by Blastocyst Complementation

Stem Cell Reports
Sanae HamanakaHiromitsu Nakauchi

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.

References

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Citations

Feb 15, 2020·Critical Reviews in Biotechnology·Cynthia Morata TarifaRosario Sánchez Pernaute
Aug 2, 2019·Current Opinion in Organ Transplantation·Graziano OldaniChristian Toso
Jun 27, 2019·Current Diabetes Reports·Tomoyuki Yamaguchi
Apr 25, 2020·Evidence-based Complementary and Alternative Medicine : ECAM·Yang LiuYunlun Li
Aug 21, 2019·Cell Transplantation·Andrew T CraneWalter C Low
Jan 12, 2021·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Enhong LiVladimir V Kalinichenko
Sep 3, 2020·American Journal of Respiratory and Critical Care Medicine·Bingqiang WenVladimir V Kalinichenko
Feb 14, 2021·Stem Cell Research & Therapy·Aleta R SteevensPeter A Santi
May 21, 2021·Stem Cell Research & Therapy·M Ruiz-EstevezO Gafni
Jun 25, 2021·Experimental Biology and Medicine·Daniel J Garry, Mary G Garry

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Methods Mentioned

BETA
Flow cytometry
fluorescence-activated cell sorting
FACS
transgenic
Genotyping
PCR
fluorescence microscopy
FCS

Software Mentioned

Excel
GraphPad Prism

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