Building human artery and vein endothelial cells from pluripotent stem cells, and enduring mysteries surrounding arteriovenous development.

Autor: Loh KM; Institute for Stem Cell Biology & Regenerative Medicine, Stanford University, Stanford, CA 94305, USA; Department of Developmental Biology, Stanford University, Stanford, CA 94305, USA. Electronic address: kyleloh@stanford.edu., Ang LT; Institute for Stem Cell Biology & Regenerative Medicine, Stanford University, Stanford, CA 94305, USA. Electronic address: layteng@stanford.edu.
Jazyk: angličtina
Zdroj: Seminars in cell & developmental biology [Semin Cell Dev Biol] 2024 Mar 01; Vol. 155 (Pt C), pp. 62-75. Date of Electronic Publication: 2023 Jun 29.
DOI: 10.1016/j.semcdb.2023.06.004
Abstrakt: Owing to their manifold roles in health and disease, there have been intense efforts to synthetically generate blood vessels in vitro from human pluripotent stem cells (hPSCs). However, there are multiple types of blood vessel, including arteries and veins, which are molecularly and functionally different. How can we specifically generate either arterial or venous endothelial cells (ECs) from hPSCs in vitro? Here, we summarize how arterial or venous ECs arise during embryonic development. VEGF and NOTCH arbitrate the bifurcation of arterial vs. venous ECs in vivo. While manipulating these two signaling pathways biases hPSC differentiation towards arterial and venous identities, efficiently generating these two subtypes of ECs has remained challenging until recently. Numerous questions remain to be fully addressed. What is the complete identity, timing and combination of extracellular signals that specify arterial vs. venous identities? How do these extracellular signals intersect with fluid flow to modulate arteriovenous fate? What is a unified definition for endothelial progenitors or angioblasts, and when do arterial vs. venous potentials segregate? How can we regulate hPSC-derived arterial and venous ECs in vitro, and generate organ-specific ECs? In turn, answers to these questions could avail the production of arterial and venous ECs from hPSCs, accelerating vascular research, tissue engineering, and regenerative medicine.
Competing Interests: Declaration of Competing Interest None.
(Copyright © 2023. Published by Elsevier Ltd.)
Databáze: MEDLINE