Recent studies on the stem cell origins of regenerating tissues have provided solid evidence in support of the role of the resident cells, rather than bone marrow-derived or transplanted stem cells, in restoring tissue architecture after an injury. This is also true for endothelial stem and progenitor cells: local pools exist in the vascular wall, and those cells are the primary drivers of vascular regeneration. This paradigm shift offers an opportunity to rethink and refine our understanding of the multiple therapeutic effects of transplanted endothelial progenitor cells, focusing on their secretome, sheddome, intercellular communicational routes, and other potential ways to rejuvenate and replenish the pool of resident cells. The dynamics of vascular wall resident cells, at least in the adipose tissue, may shed light on the origins of other cells present in the vascular wall-pericytes and mesenchymal stem cells. The fate of these cells in aging and disease awaits elucidation.
Keywords: Endothelial cell; Progenitor cells; Stem cells; Vascular development.