title: Human mesenchymal stem cells successfully improve skin-substitute wound healing.
abstract: BACKGROUND
  Large or deteriorated skin defects are sometimes life threatening. There is increasing evidence that adult stem cells are useful for tissue regeneration. Human mesenchymal stem cells (hMSCs) are self-renewing and are potent in differentiating into multiple cells and tissues.
  
  
  OBJECTIVE
  To investigate the effects of hMSCs in cutaneous wound healing.
  
  
  METHODS
  Wound healing was studied in an hMSC-populated porcine skin substitute, using a nude rat model to minimize immune reactions. Full-thickness skin and soft tissue defects of 1.5 x 1.5 cm in size, including the panniculus carnosus, were excised and covered with hMSCs and basic fibroblast growth factor (bFGF)-soaked skin substitutes and an evaluation was made of wound size, histology and protein expression at 3, 7 and 42 days after injury.
  
  
  RESULTS
  The wound size was significantly smaller in the hMSC-treated groups (P < 0.01) and any dose of bFGF (1, 10, 100 microg) enhanced the healing (P < 0.01). The re-epithelialization markers integrin alpha3 and skin-derived antileucoproteinase were remarkably increased with the presence of bFGF in a dose-dependent manner, while the mesenchymal cell surface markers CD29 and CD44 were downregulated in a time-dependent manner. Human pancytokeratin, which does not cross-react with rat antigens, was observed by Western blotting at 38 kDa and 42 kDa from the hMSC-treated tissues on day 7. The expression levels were elevated by 10 microg bFGF (P < 0.01). The immunohistochemical expression of human pancytokeratin was only observed in the hMSC-treated groups.
  
  
  CONCLUSIONS
  These data suggest that hMSCs together with bFGF in a skin defect model accelerate cutaneous wound healing as the hMSCs transdifferentiate into the epithelium.
authors: Division of Plastic and Reconstructive Surgery, Department of Developmental and Reconstructive Medicine, Nagasaki University, Graduate School of Medical and Dental Sciences, 1-7-1 Sakamoto, Nagasaki 8528501, Japan.
authors: H
authors: H
authors: Nakagawa
authors: S
authors: S
authors: Akita
authors: M
authors: M
authors: Fukui
authors: T
authors: T
authors: Fujii
authors: K
authors: K
authors: Akino
mesh_terms: D000818:Animals; D015153:Blotting, Western / Q000379:methods; D062109:Dermatologic Surgical Procedures; D004305:Dose-Response Relationship, Drug; D016222:Fibroblast Growth Factor 2 / Q000627:therapeutic use; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D039422:Integrin alpha3 / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D011923:Rats, Nude; D012867:Skin / Q000293:injuries* / Q000473:pathology; D017768:Skin, Artificial; D013552:Swine; D014945:Wound Healing / Q000187:drug effects
chemical_list: D018960:Hyaluronan Receptors; D039422:Integrin alpha3; D019012:Integrin beta1; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D016222:Fibroblast Growth Factor 2