Generation of Human Pluripotent Stem Cell-derived Endothelial Cells and Their Therapeutic Utility

Human pluripotent stem cell-derived endothelial cells (hPSC-ECs) emerged as an important source of cells for cardiovascular regeneration. This review summarizes protocols for generating hPSC-ECs and provides an overview of the current state of the research in clinical application of hPSC-derived ECs.

Various systems were developed for differentiating hPSCs into the EC lineage. Stepwise two-dimensional systems are now well established, in which various growth factors, small molecules, and coating materials are used at specific developmental stages. Moreover, studies made significant advances in clinical applicability of hPSC-ECs by removing undefined components from the differentiation system, improving the differentiation efficiency, and proving their direct vascular incorporating effects, which contrast with adult stem cells and their therapeutic effects in vivo. Finally, by using biomaterial-mediated delivery, investigators improved the survival of hPSC-ECs to more than 10 months in ischemic tissues and described long-term behavior and safety of in vivo transplanted hPSC-ECs at the histological level. hPSC-derived ECs can be as a critical source of cells for treating advanced cardiovascular diseases. Over the past two decades, substantial improvement has been made in the differentiation systems and their clinical compatibility. In the near future, establishment of fully defined differentiation systems and proof of the advantages of biomaterial-mediated cell delivery, with some additional pre-clinical studies, will move this therapy into a vital option for treating those diseases that cannot be managed by currently available therapies.