title: Studies in fat grafting: Part IV. Adipose-derived stromal cell gene expression in cell-assisted lipotransfer.
abstract: BACKGROUND
  Fat graft volume retention remains highly unpredictable, but addition of adipose-derived stromal cells to fat grafts has been shown to improve retention. The present study aimed to investigate the mechanisms involved in adipose-derived stromal cell enhancement of fat grafting.
  
  
  METHODS
  Adipose-derived stromal cells isolated from human lipoaspirate were labeled with green fluorescent protein and luciferase. Fat grafts enhanced with adipose-derived stromal cells were injected into the scalp and bioluminescent imaging was performed to follow retention of adipose-derived stromal cells within the fat graft. Fat grafts were also explanted at days 1, 5, and 10 after grafting for adipose-derived stromal cell extraction and single-cell gene analysis. Finally, CD31 immunohistochemical staining was performed on fat grafts enriched with adipose-derived stromal cells.
  
  
  RESULTS
  Bioluminescent imaging demonstrated significant reduction in luciferase-positive adipose-derived stromal cells within fat grafts at 5 days after grafting. A similar reduction in viable green fluorescent protein-positive adipose-derived stromal cells retrieved from explanted grafts was also noted. Single-cell analysis revealed expression of multiple genes/markers related to cell survival and angiogenesis, including BMPR2, CD90, CD105, FGF2, CD248, TGFß1, and VEGFA. Genes involved in adipogenesis were not expressed by adipose-derived stromal cells. Finally, CD31 staining revealed significantly higher vascular density in fat grafts explanted at day 10 after grafting.
  
  
  CONCLUSIONS
  Although adipose-derived stromal cell survival in the hypoxic graft environment decreases significantly over time, these cells provide multiple angiogenic growth factors. Therefore, improved fat graft volume retention with adipose-derived stromal cell enrichment may be attributable to improved graft vascularization.
authors.affiliation: Stanford, Calif. From the Hagey Laboratory for Pediatric Regenerative Medicine, Plastic and Reconstructive Surgery Division, Department of Surgery, Stanford University School of Medicine; and the Institute for Stem Cell Biology and Regenerative Medicine, Stanford University.
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Garza
authors.forename: Robert C
authors.initials: RC
authors.lastname: Rennert
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Paik
authors.forename: David
authors.initials: D
authors.lastname: Atashroo
authors.forename: Michael T
authors.initials: MT
authors.lastname: Chung
authors.forename: Dominik
authors.initials: D
authors.lastname: Duscher
authors.forename: Michael
authors.initials: M
authors.lastname: Januszyk
authors.forename: Geoffrey C
authors.initials: GC
authors.lastname: Gurtner
authors.forename: Michael T
authors.initials: MT
authors.lastname: Longaker
authors.forename: Derrick C
authors.initials: DC
authors.lastname: Wan
mesh_terms: D017667:Adipocytes; D000273:Adipose Tissue / Q000166:cytology* / Q000637:transplantation*; D000328:Adult; D000818:Animals; D002470:Cell Survival / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D051379:Mice; D008875:Middle Aged; D018919:Neovascularization, Physiologic / Q000235:genetics; D017154:Stromal Cells; D019737:Transplants / Q000098:blood supply