Conflicts of interest: None declared.
Human mesenchymal stem cells successfully improve skin-substitute wound healing
Article first published online: 27 JUN 2005
British Journal of Dermatology
Volume 153, Issue 1, pages 29–36, July 2005
How to Cite
Nakagawa, H., Akita, S., Fukui, M., Fujii, T. and Akino, K. (2005), Human mesenchymal stem cells successfully improve skin-substitute wound healing. British Journal of Dermatology, 153: 29–36. doi: 10.1111/j.1365-2133.2005.06554.x
- Issue published online: 5 JUL 2005
- Article first published online: 27 JUN 2005
- Accepted for publication 4 December 2004
- basic fibroblast growth factor;
- human mesenchymal stem cell;
- 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.
Objectives 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 × 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 μg) enhanced the healing (P < 0·01). The re-epithelialization markers integrin α3 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 μg 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.