Sophie Chesnoy1, Pui-Yan Lee, Leaf Huang. 1. Center for Pharmacogenetics, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
Abstract
PURPOSE: To evaluate the biologic effect of direct cutaneous TGF-beta1 gene delivery on impaired wound healing models using genetically diabetic mice. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
PURPOSE: To evaluate the biologic effect of direct cutaneous TGF-beta1 gene delivery on impaired wound healing models using genetically diabeticmice. METHODS:Diabeticmice (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. RESULTS: 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. CONCLUSION: 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 humandiabeticpatients.
Authors: G S Sidhu; H Mani; J P Gaddipati; A K Singh; P Seth; K K Banaudha; G K Patnaik; R K Maheshwari Journal: Wound Repair Regen Date: 1999 Sep-Oct Impact factor: 3.617
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