Transplantation of human embryonic stem cell-derived endothelial cells for vascular diseases

Abstract

Using endothelial cells for therapeutic angiogenesis/vasculogenesis of ischemia diseases has led to exploring human embryonic stem cells (hESCs) as a potentially unlimited source for endothelial progenitor cells. With their capacity for self-renewal and pluripotency, hESCs and their derived endothelial cells (hESC-ECs) may be more advantageous than other endothelial cells obtained from diseased populations. However, hESC-ECs' poor differentiation efficiency and poorly characterized in vivo function after transplantation present significant challenges for their future clinical application. This review will focus on the differentiation pathways of hESCs and their therapeutic potential for vascular diseases, as well as the monitoring of transplanted cells' fate via molecular imaging. Finally, cell enhancement strategies to improve the engraftment efficiency of hESC-ECs will be discussed.

Fig. 1

Generation of human embryonic stem cell-derived endothelial cells (hESC-ECs) by two-dimensional (2D) or three-dimensional (3D) culture. The hESCs are differentiated in monolayer (2D) or embryoid body (3D) culture. The endothelial cells are isolated and subcultured. Afterwards, hESC-ECs can form tube-like structure in vitro (left) as well as small blood vessels in vivo in Matrigel plug (right). Green represents GFP and red represents CD31 staining. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]

Fig. 2

Conceptual basis of tracking the survival of transplanted stem cells in living animals. hESCs are first stably transduced with a reporter gene such as firely luciferase. After endothelial differentiation, hESC-ECs are then transplanted into the myocardial ischemia or hindlimb ischemia model. In the presence of reporter probe d-luciferin, the cells can emit photons that can be detected by a highly sensitive charged coupled device (CCD) camera. Cell survival and migration can then be tracked longitudinally within the same animal. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]

Fig. 3

A combination strategy for increasing the engraftment of hESC-ECs by biomatrix and growth factors. This schematic depicts a composite of injectable and biodegradable scaffolds with hESC-ECs and pro-survival growth factors. The hESC-ECs can differentiate into blood vessels with pericyte. The growth factors can promote cardiac stem cells (CSC) from the peri-infarction region or bone marrow mononuclear cells (MNC) in the circulation to migrate into the infarcted zone to regenerate cardiomyocytes or blood vessels. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]