Stem/Progenitor Cells in Vascular Regenerative Medicine: Mechanisms, Signalling and Translation

Endothelial cells (ECs) and smooth muscle cells (SMCs) play pivotal roles in maintaining vascular homeostasis. Their dysregulations are critical in the pathogenesis of various disease processes such as atherosclerosis which leads to severe cardiovascular diseases such as coronary heart disease and stroke. Vascular regeneration serves as an effective therapeutic strategy for these diseases. The therapeutic prospect of stem cell-based therapy, given the capacity of stem cells to replicate, to differentiate and to directly form new blood vessels, represents the ideal approach for vascular regeneration. The identification of adult stem/progenitor cells in both circulating blood and on the vessel wall indicates that endogenous stem cells have the capacity to repair injured endothelium and restore vascular homeostasis. On the other hand, pluripotent stem cells (PSCs), which have eminent capacity for selfrenewal, represent the ideal candidates in regenerative medicine. There are enormous excitements surrounding the prospect of generating functional vascular cells through activating vascular lineage differentiation of PSCs (such as embryonic stem cells (ESCs) and induced PSCs (iPSCs)) for clinical cell therapy. Recent advances in induced lineage conversion from fibroblasts to ECs and SMCs present another exciting strategy in vascular regeneration. Progresses in vascular tissue engineering have further complemented the vascular differentiation and grafting of reprogrammed vascular lineage cells onto the sites of vessel injury, through scaffolds made with native matrices, synthetic polymers or decellularised tissues. Finally, the progresses made in generating more origin-specific vascular cells from patient-derived iPSCs have enabled researchers in uncovering new insights on the molecular mechanisms underlying various vascular diseases, as well as for drug discovery, drug screening, toxicity testing and personalised medicine delivery. In this chapter, we will describe different strategies and highlight the recent efforts in generating functional vascular cells from various populations of stem and progenitor cells, their underlying molecular mechanisms, and their roles in therapeutic vascular regeneration. With the field of regenerative medicine moving in an accelerating pace, the prospect of using stem and progenitor cells clinically for vascular regeneration in treating vascular and ischemic diseases is on the horizon.

Keywords: Embryonic stem cells, Endothelial cells, Induced pluripotent stem cells, Ischemic diseases, Lineage conversion, Stem cells, Tissue engineered blood vessels, Transdifferentiation, Vascular differentiation, Vascular progenitor cells, Vascular regeneration, Vascular smooth muscle cells.