Human mesenchymal stem cells successfully improve skin-substitute wound healing.
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.
Nakagawa
H
H
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.
Akita
S
S
Fukui
M
M
Fujii
T
T
Akino
K
K
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
D018960:Hyaluronan Receptors; D039422:Integrin alpha3; D019012:Integrin beta1; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D016222:Fibroblast Growth Factor 2