The pivotal role of VEGF in adipose-derived-stem-cell-mediated regeneration

Importance of the field: Several lines of evidence suggest that VEGF is a key regulator of the paracrine effects of adipose-derived stem cells (ASCs), but the mechanism of action remains to be identified. Areas covered in this review: This brief review discusses the following research questions: i) Does VEGF increase the proliferation/migration and differentiation of ASCs?; ii) Does VEGF mediate the paracrine effects of ASCs?; and iii) How is VEGF synthesized, and which factors regulate VEGF secretion? What the reader will gain: External stimuli such as hypoxia may activate receptor tyrosine kinases in the membrane of ASCs, which, in turn, phosphorylate extracellular signal regulated kinase (ERK) and members of the Akt signaling pathway, stabilizing hypoxia inducible factor 1 alpha (HIF-1 alpha) that are primary regulators of VEGF expression. Secreted VEGF directly stimulates ASCs via VEGF receptors in an autocrine manner and regenerates damaged neighboring cells in a paracrine manner. Take home message: Most studies of stem cell regeneration have focused on differentiation of ASCs and their building block function; however, the paracrine effects of ASCs should also be the focus of attention.