title: Human tissue-resident stem cells combined with hyaluronic acid gel provide fibrovascular-integrated soft-tissue augmentation in a murine photoaged skin model.
abstract: BACKGROUND
  Transplantation of adipose tissue-resident mesenchymal stem cells has been found to contribute to the establishment of a supportive fibrovascular network. The authors sought to evaluate the potential of human adipose tissue-derived stem cells to integrate with nonanimal stabilized hyaluronic acid as a novel injectable soft-tissue filler.
  
  
  METHODS
  Cell proliferation was measured by bromodeoxyuridine incorporation. Interactions of adipose tissue-derived stem cells with hyaluronic acid were documented by scanning electron microscopy. The effect of this combination on procollagen mRNA was assessed by real-time polymerase chain reaction. The potential therapeutic effects were evaluated in an athymic murine photoaged skin model by histology and by high-resolution magnetic resonance imaging. Angiogenesis was assessed by microvessel density analysis.
  
  
  RESULTS
  Under in vitro culture conditions, the authors found an equal proliferation capacity of adipose tissue-derived stem cells grown on hyaluronic acid versus controls. Scanning electron microscopy showed enhanced establishment of complex microvillous networks in adipose tissue-derived stem cells adherent to hyaluronic acid compared with controls. Adipose tissue-derived stem cells and hyaluronic acid induced a significant increase in procollagen 1-alpha-2 mRNA expression compared with controls. In an athymic murine photoaged skin model, injection of this combination ablated photoinduced skin wrinkles. Magnetic resonance imaging revealed a consistent and stable volume fill by adipose tissue-derived stem cells and nonanimal stabilized hyaluronic acid at 3 weeks. Adipose tissue-derived stem cells actively incorporated into the hyaluronic acid fill and showed an organized fibrovascular network at 3 weeks.
  
  
  CONCLUSIONS
  The combination of adipose tissue-derived stem cells and nonanimal stabilized hyaluronic acid holds promise as a tool with which to achieve lasting volume fill in reconstructive surgical soft-tissue augmentation.
authors.affiliation: Houston, Texas; and Magdeburg, Germany From the Departments of Molecular Pathology and Plastic Surgery, University of Texas M. D. Anderson Cancer Center; the Department of Radiology, Otto von Guericke University; and InGeneron Inc.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Altman
authors.forename: Feras J
authors.initials: FJ
authors.lastname: Abdul Khalek
authors.forename: Max
authors.initials: M
authors.lastname: Seidensticker
authors.forename: Severin
authors.initials: S
authors.lastname: Pinilla
authors.forename: Yasheng
authors.initials: Y
authors.lastname: Yan
authors.forename: Micheal
authors.initials: M
authors.lastname: Coleman
authors.forename: Yao-Hua
authors.initials: YH
authors.lastname: Song
authors.forename: Charles E
authors.initials: CE
authors.lastname: Butler
authors.forename: Eckhard U
authors.initials: EU
authors.lastname: Alt
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D049109:Cell Proliferation; D049452:Green Fluorescent Proteins; D006801:Humans; D006820:Hyaluronic Acid; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D051379:Mice; D008819:Mice, Nude; D008855:Microscopy, Electron, Scanning; D008871:Microvilli; D018919:Neovascularization, Physiologic; D012867:Skin / Q000473:pathology; D015595:Skin Aging; D017695:Soft Tissue Injuries; D013234:Stem Cells / Q000166:cytology; D017154:Stromal Cells; D054457:Tissue Scaffolds
chemical_list: D049452:Green Fluorescent Proteins; D006820:Hyaluronic Acid