Abstract
Inadequate supply of oxygen (O2) is a hallmark of many diseases, in particular those related to the cardiovascular system. On the other hand, tissue hypoxia is an important factor regulating (normal) embryogenesis and differentiation of stem cells at the early stages of embryonic development. In culture, hypoxic conditions may facilitate the derivation of embryonic stem cells (ESCs) and the generation of induced pluripotent stem cells (iPSCs), which may serve as a valuable tool for disease modeling. Endothelial cells (ECs), multifunctional components of vascular structures, may be obtained from iPSCs and subsequently used in various (hypoxia-related) disease models to investigate vascular dysfunctions. Although iPSC-ECs demonstrated functionality in vitro and in vivo, ongoing studies are conducted to increase the efficiency of differentiation and to establish the most productive protocols for the application of patient-derived cells in clinics. In this review, we highlight recent discoveries on the role of hypoxia in the derivation of ESCs and the generation of iPSCs. We also summarize the existing protocols of hypoxia-driven differentiation of iPSCs toward ECs and discuss their possible applications in disease modeling and treatment of hypoxia-related disorders.
Highlights
The fundamental importance of adequate oxygenation for the functioning of aerobic organisms has been recognized for centuries, and the efforts to understand the molecular mechanisms of cell sensing and adopting to oxygen availability were awarded the 2019 Nobel Prize in Physiology or Medicine, to William G
Already in 2007, the group of Chung et al [85,86] found that the central region of human embryonic stem cells (hESCs)-derived human embryoid bodies (EB) is enriched in cells that express Endothelial cells (ECs) markers, including platelet endothelial cell adhesion molecule-1 (PECAM1), vWF, VEGFR1, Tie2, which can uptake acetylated low-density lipoproteins and exhibit increased differentiation capacity toward EC lineage
After 6 days: CD34, VEGFR2, CD56 mRNA Primed and continuous: CD144, PECAM1 mRNA; PECAM1+ cells; lectin binding, uptake of acetylated low-density lipoproteins (acLDL), tube formation on Matrigel Continuous: endothelial-like morphology with bundles of elongated cells and cobblestone area-forming cells; CD144+ cells; CD144 and PDGFRβ localized with CD144+ clusters surrounded by PDGFRβ+ cells hESC and human induced pluripotent stem cells (hiPSCs) cells grown on an inactivated mouse embryonic feeder layer in a growth medium consisting of 80% ES-DMEM/F12 supplemented with 20% KSR and FGF2
Summary
The fundamental importance of adequate oxygenation for the functioning of aerobic organisms has been recognized for centuries, and the efforts to understand the molecular mechanisms of cell sensing and adopting to oxygen availability were awarded the 2019 Nobel Prize in Physiology or Medicine, to William G. Embryonic development and the maintenance of adult homeostasis is dependent on the delivery of adequate O2 and nutrients to cells in the body via a functional vascular system. In contrast to atmospheric oxygen concentration (21%), its level in tissues is much lower and varies between organs. The development of human induced pluripotent stem cells (hiPSCs) [2] has opened a new era in the studies of molecular aspects of human diseases. Patient-specific hiPSCs may provide mechanistic insights into specific disorders, those which are hypoxia-driven. They have other numerous biomedical applications in basic research and after directed differentiation into derivatives of all three germ layers can serve as a platform for drug testing
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
