Advances in pluripotent stem cell-derived endothelial cells: from biomaterials to organ regeneration.

Human embryonic stem cells (ESCs), by virtue of their capability to self-renew and differentiate into a variety of cell types, represent the first type of pluripotent stem cells (PSCs) to be used in clinical transplantation during recent phase-I trials; however, it is still unclear whether hESC-derived tissues can self-organize and form part of the vascularized, functional organ following transplantation. Recently, endothelial cells (ECs) or angiogenic factors such as VEGFA have been demonstrated to support development and regeneration of multiple organ systems, including the heart, pancreas, liver, lung and bone marrow. Therefore, co-transplantation of ECs derived from the same parental PSCs that differentiate into cell types of interest; or overexpression of the inductive angiogenic factors responsible for organ regeneration might be beneficial to support function of hPSC-derived tissues. In this special issue, we discuss how protein kinases (Ng and colleagues); DNA methylation and histone modification (Tsui and colleagues) regulate cellular pluripotency and cell-fate specification of PSCs. In addition, we discuss how ECs and angiogenic factors could contribute to repair and regeneration of organs such as the heart (Yuan and colleagues), the cardiovascular system (Tse and colleagues) and the pancreas (Lui). We also discuss the role of mesenchymal stem cells or paracrine factors secreted by them in tissue repair (Li and colleagues). Lastly, we discuss how to generate self-organized and vascularized tissues derived from PSCs in a 2- or 3-dimensional format by fusing tissue bioengineering approaches with stem cell technology (Chen).