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Role of insulin-like growth factors in endothelium differentiation


ECs derived from stem cells are the beginning of vasculogenesis.  Vasculogenesis is the new production of a vascular network from mesodermal progenitor cells. This can be distinguished from angiogenesis, which is the creation of new capillaries from vessels that already exist through the process of splitting or sprouting. This can occur "in vitro" in embryoid bodies (EB) derived from embryonic stem cells; this process in EB is similar to "in vivo" vasculogenesis. Important signaling factors for vasculogenesis are TGF-β, BMP4, and VEGF, all of which promote pluripotent stem cells to differentiate into mesoderm, endothelial progenitor cells, and then into mature endothelium.
It is well established that insulin-like growth factor (IGF) signaling is important for cell responses such as mitogenesis, cell growth, proliferation, angiogenesis, and differentiation. IGF1 and IGF2 increase the production of ECs in EB. A method that IGF employs to increase vasculogenesis is upregulation of VEGF. Not only is VEGF critical for mesoderm cells to become an EC, but also for EPCs to differentiate into mature endothelium. Understanding this process can lead to further research in vascular regeneration. 

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