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

Abstract

Purpose of Review 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. Recent Findings 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. Summary 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.

Coculture of Endothelial Cells with Human Pluripotent Stem Cell‐Derived Cardiac Progenitors Reveals a Differentiation Stage‐Specific Enhancement of Cardiomyocyte Maturation

“…When Nolan et al engrafted generic, stem cell‐derived ECs into mouse kidneys and livers, they found that the ECs acquired the expression of markers specific to the tissue in which the cells were engrafted. The hPSC‐derived ECs used in this study arise from a mesoderm progenitor but lack tissue and vessel‐type specificity, which may result from developmental immaturity . It would be interesting to determine whether cardiac specificity is induced in these hPSC‐derived ECs cocultured with hPSC‐derived CPCs or CMs and if this specification has an impact on the observed CM maturation.…”

Bioengineering strategies for the treatment of peripheral arterial disease

“…For example, the group of Lee et al have demonstrated that a biocompatible peptide amphiphile (PA) nanomatrix hydrogel substantially improved long-term survival of human pluripotent stem cell (hPSC)-derived ECs in an ischemic hindlimb environment (>10 months). The hPSC-derived ECs, when encapsulated into PA hydrogel, showed better perfusion recovery and higher and more prolonged angiogenic and vascular incorporation capabilities than the bare hPSC-derived ECs [ 29 , 30 ].…”

Bioactive Molecules for Skin Repair and Regeneration: Progress and Perspectives

“…For example, high differentiation efficiency was achieved when CHIR99021 was combined with a lower concentration of VEGF-A and DLL4 (a Notch ligand) in the endothelial cell induction system [66]. DLL4 could enhance endothelial celllineage differentiation and inhibit hematopoietic-lineage differentiation [67]. In addition, CHIR99021 in combination with FGF2, VEGF, and BMP4 could synergistically induce early vascular progenitors (VPs) from hiPSCs with high purities.…”