Intradermal injection of transforming growth factor-beta1 gene enhances wound healing in genetically diabetic mice.

Abstract

To evaluate the biologic effect of direct cutaneous TGF-beta1 gene delivery on impaired wound healing models using genetically diabetic mice. Diabetic mice (C57BKS.Cg-m +/+ Leprdb female mice) with 1 cm x 1 cm excisional wounds were intradermally injected with 60 microg of plasmid DNA encoding TGF-beta1 gene. The wound closure was measured up to 14 days postwounding. At days 7 and 14 postwounding, sections of skin were taken for hematoxylin and eosin and Masson's trichome staining to examine the morphology and collagen deposition. The cell proliferation and TGF-beta1 gene expression were studied using immunohistochemical stainings for 5-bromo-2-deoxyuridine and for TGF-beta1. A higher cell proliferation rate and a denser and more organized new extracellular matrix were observed in the treated wound site. Complete wound closure was detected as early as 7 days for TGF-beta1-treated group in comparison with 11-14 days for the untreated, control plasmid DNA- and PBS-treated groups. A single intradermal injection of TGF-beta1 plasmid DNA was sufficient to enhance wound healing. This approach represents a new strategy that may be applied to the treatment of excisional wounds in human diabetic patients.