title: Studies in adipose-derived stromal cells: migration and participation in repair of cranial injury after systemic injection.
abstract: BACKGROUND
  Adipose-derived stromal cells are a multipotent cell type with the ability to undergo osteogenic differentiation. The authors sought to examine whether systemically administered adipose-derived stromal cells would migrate to and heal surgically created defects of the mouse cranial skeleton.
  
  
  METHODS
  Mouse adipose-derived stromal cells were harvested from luciferase-positive transgenic mice; human adipose-derived stromal cells were harvested from human lipoaspirate and labeled with luciferase and green fluorescent protein. A 4-mm calvarial defect (critical sized) was made in the mouse parietal bone; skin incisions alone were used as a control (n = 5 per group). Adipose-derived stromal cells were injected intravenously (200,000 cells per animal) and compared with saline injection only. Methods of analyses included micro-computed tomographic scanning, in vivo imaging system detection of luciferase activity, and standard histology.
  
  
  RESULTS
  Migration of adipose-derived stromal cells to calvarial defect sites was confirmed by accumulation of luciferase activity and green fluorescent protein stain as early as 4 days and persisting up to 4 weeks. Little activity was observed among control groups. Intravenous administration of either mouse or human adipose-derived stromal cells resulted in histologic evidence of bone formation within the defect site, in comparison with an absence of bone among control defects. By micro-computed tomographic analysis, human but not mouse adipose-derived stromal cells stimulated significant osseous healing.
  
  
  CONCLUSIONS
  Intravenously administered adipose-derived stromal cells migrate to sites of calvarial injury. Thereafter, intravenous human adipose-derived stromal cells contribute to bony calvarial repair. Intravenous administration of adipose-derived stromal cells may be an effective delivery method for future efforts in skeletal regeneration.
authors.affiliation: Stanford, Calif. From the Hagey Pediatric Regenerative Research Laboratory, Department of Surgery, Plastic and Reconstructive Surgery Division, and the Department of Medicine and Radiology, Stanford University School of Medicine.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Levi
authors.forename: Aaron W
authors.initials: AW
authors.lastname: James
authors.forename: Emily R
authors.initials: ER
authors.lastname: Nelson
authors.forename: Shijun
authors.initials: S
authors.lastname: Hu
authors.forename: Ning
authors.initials: N
authors.lastname: Sun
authors.forename: Michelle
authors.initials: M
authors.lastname: Peng
authors.forename: Joseph
authors.initials: J
authors.lastname: Wu
authors.forename: Michael T
authors.initials: MT
authors.lastname: Longaker
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D002454:Cell Differentiation; D002465:Cell Movement; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D010012:Osteogenesis / Q000502:physiology*; D010294:Parietal Bone / Q000293:injuries* / Q000473:pathology; D033581:Stem Cell Transplantation / Q000379:methods*; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism*; D014945:Wound Healing / Q000502:physiology*