title: Paracrine mechanism of angiogenesis in adipose-derived stem cell transplantation.
abstract: BACKGROUND
  Adipose-derived stem cells (ASCs) have shown potential for cell-based therapy in the field of plastic surgery. However, the fate of ASCs after transplantation and the mechanism(s) of their biologic capabilities remain unclear.
  
  
  METHODS
  We isolated and cultured ASCs from transgenic mice that express both luciferase and green fluorescent protein and injected the cells into the inguinal fat pads of wild-type mice. We tested 4 experimental groups, namely, ischemic fat pads with/without ASCs and control fat pads with/without ASCs.
  
  
  RESULTS
  Transplanted ASCs were tracked with bioluminescence imaging. The luminescence gradually decreased over 28 days, indicating cell death after transplantation. More ASCs were retained in ischemic fat pads on day 7 compared to control fat pads. On day 14, adipose tissue vascular density was higher in the ASC transplantation groups compared to those without ASCs. On day 28, there was decreased atrophy of adipose tissue in ASC-treated ischemic fat pads. Transplanted ASCs were detected as nonproliferating green fluorescent protein-positive cells, whereas native endothelial cells adjacent to the transplanted ASCs were proliferative. Protein analysis demonstrated higher expression of hepatocyte growth factor and vascular endothelial growth factor in the ASC transplantation groups, suggesting a paracrine mechanism, which was confirmed by in vitro experiments with conditioned media from ASCs.
  
  
  CONCLUSIONS
  Transplanted ASCs are preferentially retained in ischemic adipose tissue, although most of the cells eventually undergo cell death. They exert an angiogenic effect on adipose tissue mainly through a paracrine mechanism. Increased understanding of these effects will help develop ASCs as a tool for cell-based therapy.
authors: From the Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University, Stanford, CA.
authors: Hirotaka
authors: H
authors: Suga
authors: Jason P
authors: JP
authors: Glotzbach
authors: Michael
authors: M
authors: Sorkin
authors: Michael T
authors: MT
authors: Longaker
authors: Geoffrey C
authors: GC
authors: Gurtner
mesh_terms: D000273:Adipose Tissue / Q000098:blood supply* / Q000166:cytology / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D049109:Cell Proliferation; D002470:Cell Survival; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D007150:Immunohistochemistry; D007511:Ischemia; D008163:Luminescent Measurements; D051379:Mice; D008822:Mice, Transgenic; D018919:Neovascularization, Physiologic / Q000502:physiology*; D019899:Paracrine Communication; D033581:Stem Cell Transplantation / Q000379:methods*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D015415:Biomarkers; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D017228:Hepatocyte Growth Factor
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