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


METHODS
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?


RESULTS
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 1α (HIF-1α) 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.


CONCLUSIONS
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.
Song
Seung-Yong
SY
Department of Plastic & Reconstructive Surgery, CHA University, CHA Bundang Medical Center, Seongnam-si, Gyeonggi-do, Korea.
Chung
Hyung-Min
HM
Sung
Jong-Hyuk
JH
D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D019898:Autocrine Communication / Q000502:physiology; D001927:Brain Diseases / Q000601:surgery; D002454:Cell Differentiation; D002455:Cell Division; D002465:Cell Movement; D002470:Cell Survival; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000502:physiology; D007511:Ischemia / Q000601:surgery; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051379:Mice; D008819:Mice, Nude; D018919:Neovascularization, Physiologic; D019899:Paracrine Communication / Q000502:physiology; D051381:Rats; D040262:Receptors, Vascular Endothelial Growth Factor / Q000502:physiology; D012038:Regeneration / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000737:chemistry / Q000502:physiology*; D014945:Wound Healing
C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D040262:Receptors, Vascular Endothelial Growth Factor