Induced Pluripotent Stem Cell-Derived Endothelial Cells: Overview, Current Advances, Applications, and Future Directions

Abstract

Endothelial cells are prevalent in our bodies and serve multiple functions. By lining the vasculature, they provide a barrier to tissues and facilitate the transport of molecules and cells. They also maintain hemostasis and modulate blood flow by reacting to chemokines and releasing signal molecules. Thus, endothelial dysfunction leads to a wide variety of diseases, including atherosclerosis and coronary artery disease. In today's era of stem cell research, induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) have emerged for research and engineering purposes. They are not only tools for studying disease states but are also a crucial part of efforts to engineer vessel and organ grafts. As the techniques in cell culture, microfluidics, and personalized medicine concomitantly improve, the potential for iPSC-ECs is enormous. We review functions of endothelium in our bodies, the development and uses of iPSC-ECs, and the possible avenues to explore in the future.

Figure 1

Schematic shows the important features of endothelial cell function. The left side of the figure highlights thromboregulation, with the left-most endothelial cell in the resting state promoting fibrinolysis and inhibiting the clotting cascade and platelet aggregation. The endothelial cell adjacent is in the active state with release of von Willebrand factor (vWF) from Weibel-Palade body and release of platelet-activating factor (PAF). vWF also initiates the clotting cascade when the subendothelium is exposed. On the right side, the immune function of endothelial cells is illustrated. A leukocyte rolls by binding to the selectin molecules expressed on the surface of endothelial cells, adheres via intercellular adhesion molecule 1 (ICAM-1; and vascular cell adhesion molecule 1, not illustrated), and migrates into the tissue. NO, nitric oxide; PECAM, platelet endothelial cell adhesion molecule 1; PGI2, prostaglandin I2; tPA, tissue plasminogen activator.