Hui Shi
Juanjuan Zhou
Qingjian Zou
Quanjun Zhang
Shixue Gou
Pengfei Chen
Lisha Mou
Nana Fan
Yangyang Suo
Zhen Ouyang
Chengdan Lai
Quanmei Yan
Liangxue Lai
aCAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China
bUniversity of Chinese Academy of Sciences, Beijing, 100049, China
cGuangzhou Regenerative Medicine and Health Guangdong Laboratory (GRMH-GDL), Guangzhou, 510005, China
dInstitute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, 100101, China
eResearch Unit of Generation of Large Animal Disease Models, Chinese Academy of Medical Sciences (2019RU015), Guangzhou, 510530, China
fSchool of Biotechnology and Health Sciences, Wuyi University, Jiangmen, 529020, China
gShenzhen Xenotransplantation Medical Engineering Research and Development Center, Institute of Translational Medicine, Shenzhen University Health Science Center, Shenzhen University School of Medicine, First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, 518035, China
hDepartment of Central Laboratory, Shenzhen Longhua District Central Hospital, Shenzhen, 518110, China
iSchool of Life Sciences, University of Science and Technology of China, Hefei, 230027, China
jJoint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, 511436, China
More InformationCorresponding author: E-mail address: yan_quanmei@gibh.ac.cn (Quanmei Yan);E-mail address: lai_liangxue@gibh.ac.cn (Liangxue Lai)
Publish Date:2020-05-25
Abstract
Abstract
Interspecies chimera through blastocyst complementation could be an alternative approach to create human organs in animals by using human pluripotent stem cells. A mismatch of the major histocompatibility complex of vascular endothelial cells between the human and host animal will cause graft rejection in the transplanted organs. Therefore, to achieve a transplantable organ in animals without rejection, creation of vascular endothelial cells derived from humans within the organ is necessary. In this study, to explore whether donor xeno-pluripotent stem cells can compensate for blood vasculature in host animals, we generated rat-mouse chimeras by injection of rat embryonic stem cells (rESCs) into mouse blastocysts with deficiency of Flk-1 protein, which is associated with endothelial and hematopoietic cell development. We found that rESCs could differentiate into vascular endothelial and hematopoietic cells in the rat-mouse chimeras. The whole yolk sac (YS) of Flk-1 rat-mouse chimera was full of rat blood vasculature. Rat genes related to vascular endothelial cells, arteries, and veins, blood vessels formation process, as well as hematopoietic cells, were highly expressed in the YS. Our results suggested that rat vascular endothelial cells could undergo proliferation, migration, and self-assembly to form blood vasculature?and that hematopoietic cells could differentiate into B cells, T cells, and myeloid cells in rat-mouse chimeras, which was able to rescue early embryonic lethality caused byFlk-1 deficiency in mouse.Keywords: Blastocyst complementation,
Interspecies chimera,
Intraspecies chimera,
Vascular endothelial cell,
Hematopoietic cell
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