Endothelial Cells Derived From Nuclear Reprogramming

Abstract

The endothelium plays a pivotal role in vascular homeostasis, regulating the tone of the vascular wall, and its interaction with circulating blood elements. Alterations in endothelial functions facilitate the infiltration of inflammatory cells and permit vascular smooth muscle proliferation and platelet aggregation. Therefore, endothelial dysfunction is an early event in disease processes including atherosclerosis, and because of its critical role in vascular health the endothelium is worthy of the intense focus it has received. However, there are limitations to studying human endothelial function in vivo, or human vascular segments ex vivo. Thus, methods for endothelial cell culture have been developed and refined. More recently, methods to derive endothelial cells from pluripotent cells have extended the scientific range of human endothelial cell studies. Pluripotent stem cells may be generated, expanded and then differentiated into endothelial cells for in vitro studies. Constructs for molecular imaging can also be employed to facilitate tracking these cells in vivo. Furthermore, one can generate patient-specific endothelial cells to study the effects of genetic or epigenetic alterations on endothelial behavior. Finally, there is the opportunity to apply these cells for vascular therapy. This review focuses on the generation of endothelial cells from stem cells; their characterization by genetic, histological and functional studies; and their translational applications.

Conversion of Human Fibroblasts to Functional Endothelial Cells by Defined Factors

“…17 Therefore, we characterized the endothelial identity of the iEnd cells based on their functional capacity to form capillary lumens when embedded subcutaneously within matrigel plugs in SCID mice. At two weeks post implantation, histological analysis demonstrated that the iEnd cells within plugs maintained expression of human-specific CD31 and could organize to form capillaries (Figure 1G), whereas the parental fibroblasts neither expressed CD31 nor formed tubular structures in vivo .…”

Patterns of expression of factor VIII and von Willebrand factor by endothelial cell subsets in vivo

“…The identification of these FVIII-producing EC subtypes makes it possible to elucidate the genetic determinants that regulate FVIII synthesis. Moreover, LECs can be cultured or generated from induced pluripotent stem cells 47,48 and are accessible for therapeutic manipulation and transplantation 49 : they may serve as an ideal cell source or target for cell-or gene-based FVIII therapy for hemophilia A.…”

Modulating the Vascular Response to Limb Ischemia

“…Clinical studies using these cell sources are now required to determine whether these cell sources provide advantages compared with prior cell types. 127–131 …”