Human Induced Pluripotent Stem Cell-Derived Vascular Cells: Recent Progress and Future Directions

Abstract

Human induced pluripotent stem cells (hiPSCs) hold great promise for cardiovascular regeneration following ischemic injury. Considerable effort has been made toward the development and optimization of methods to differentiate hiPSCs into vascular cells, such as endothelial and smooth muscle cells (ECs and SMCs). In particular, hiPSC-derived ECs have shown robust potential for promoting neovascularization in animal models of cardiovascular diseases, potentially achieving significant and sustained therapeutic benefits. However, the use of hiPSC-derived SMCs that possess high therapeutic relevance is a relatively new area of investigation, still in the earlier investigational stages. In this review, we first discuss different methodologies to derive vascular cells from hiPSCs with a particular emphasis on the role of key developmental signals. Furthermore, we propose a standardized framework for assessing and defining the EC and SMC identity that might be suitable for inducing tissue repair and regeneration. We then highlight the regenerative effects of hiPSC-derived vascular cells on animal models of myocardial infarction and hindlimb ischemia. Finally, we address several obstacles that need to be overcome to fully implement the use of hiPSC-derived vascular cells for clinical application.

Proteomics of novel induced pluripotent stem cell-derived vascular endothelial cells reveal extensive similarity with an immortalized human endothelial cell line

“…At this stage, stem cell leukemia (SCL) and the adherens junction protein vascular endothelial (VE)-cadherin, markers of endothelial precursors, are also induced. Flk1 / SCL + hemangioblasts within the mesoderm form blood island clusters and are induced by vascular endothelial growth factor (VEGF)-A ( 31 ), a critical morphogen known to drive specification of vascular endothelium ( 41 ). In this study, we used these critical morphogens, namely FGF2, BMP4, and VEGF-A, to induce vascular endothelial cell progenitors from mesodermal cells.…”

3D culturing of human pluripotent stem cells-derived endothelial cells for vascular regeneration

“…Human pluripotent stem cells-derived endothelial cells may be ideal for therapeutic neovascularization of ischemic tissues; these can meet therapeutic expectations only if they possess sufficient functional activity to support the physiological mechanisms of the vascular system. Human PSC-EC is readily available as undifferentiated hPSC and can be efficiently differentiated towards endothelial lineage using established protocols 15 - 17 . Intravenously administered iPSC-derived Flk1 + cells were shown to be recruited to the site of vascular injury, enhancing reendothelialization and suppressing neointimal hyperplasia 18 .…”

Understanding genomic medicine for thoracic aortic disease through the lens of induced pluripotent stem cells

“…Attempts to use iPSCs to model vascular cell types began in the late 2000s (93, 94) resulting in a mix of several cells including VSMCs and endothelial cells (ECs), in a form of co-culture. Since then, a large number of protocols have been described using highly defined media with small molecules or cytokine cocktails to drive differentiation [several of which are well summarised in these reviews (95)(96)(97)] that claim to have successfully produced VSMCs or ECs of high purities, organ-specific, developmentally pertinent lineages (73,76) and fine-tuned phenotypic states including the contractile one (37,98,99).…”