Role of Notch1 in the arterial specification and angiogenic potential of mouse embryonic stem cell-derived endothelial cells

Stem Cell Research & Therapy
Jae Kyung ParkJae Ho Kim

Abstract

Endothelial cells have been shown to mediate angiogenesis in ischemic injury sites and contribute to the repair of damaged tissues. However, the treatment of ischemic disease requires a significant number of endothelial cells, which are difficult to isolate from patients. Embryonic stem cells have been considered a potential source of therapeutic cells due to their unlimited self-renewal and pluripotent properties. With regard to vascular development, Notch1 has been established as a key regulator of the specification of arterial endothelial cells. Using a doxycycline-induced expression system of the intracellular domain of Notch1, we explored the role of Notch1 in the differentiation of embryonic stem cells to arterial endothelial cells. The therapeutic effect of the arterial endothelial cells was investigated in a murine hindlimb ischemia model. The blood perfusion rate in the ischemic limb was determined by laser Doppler perfusion imaging, and vasculogenesis was quantified using immunocytochemistry. Induced expression of the intracellular domain of Notch1 increased the levels of endothelial markers, such as CD31 and VE-cadherin, in differentiated endothelial cells. Induction of intracellular domain of Notch1 stimulated expre...Continue Reading

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Citations

Nov 5, 2019·Current Stem Cell Research & Therapy·L Vinod Kumar ReddyDwaipayan Sen
Jan 8, 2020·Cells·Simone PolvaniAndrea Galli
Jun 12, 2021·Differentiation; Research in Biological Diversity·Xuechun LiYu Zhang
Jul 11, 2021·Proceedings of the National Academy of Sciences of the United States of America·Tobias DeuseSonja Schrepfer
Jul 24, 2021·American Journal of Physiology. Heart and Circulatory Physiology·Sanghamitra SahooPatrick J Pagano

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Methods Mentioned

BETA
FACS
fluorescence-activated cell sorter
electrophoresis
fluorescence microscopy
confocal microscopy
magnetic-activated

Software Mentioned

CellQuest
ImageJ

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