Type of Document	Dissertation
Author	Lee, Pui-yan R
Author's Email Address	prlst4@pitt.edu
URN	etd-07242005-181117
Title	Cell/Gene Therapy For Diabetic Wound Healing
Degree	Doctor of Philosophy
Program	Bioengineering
School	School of Engineering
Advisory Committee	Advisor Name Title Leaf Huang Committee Chair Johnny Huard Committee Member Kacey Marra Committee Member Patricia Hebda Committee Member
Keywords	Naked DNA Stem cells Thermosensitive Hydrogel Diabetic Wound Healing Electroporation
Date of Defense	2005-07-20
Availability	unrestricted
Abstract Wounds in diabetes are difficult to heal. Current standard strategy employs series of medical treatments to clean and remove the infected tissue, and keep moisture with adequate blood supply. However, the standard treatments may not be sufficient enough. According to ADA, there are an increasing number of amputation cases in diabetes. In this thesis, recent development of therapies in wound healing is reviewed and results of using a TGF-ƒÒ1 plasmid DNA or stem cells in genetically diabetic mouse model are reported. In previous study, we have found that the diabetic wound healing has been improved by intradermally injecting TGF-ƒÒ1 plasmid DNA. This finding supports the feasibility of using naked DNA as a therapeutic approach for treating diabetic wounds. Since naked DNA approach yields low efficiency of gene transfer, we seek strategies that can enhance the gene expression. Hydrogel as well as electroporation which involves an application of electric pulses has been shown to enhance gene transfection. On the other hand, electrical stimulation (ES) which involves the application of a different condition of electric pulses from electroporation or hydrogel wound dressing has been shown to improve wound healing. In this thesis project, we develop a more effective strategy to improve diabetic wound healing by combining the available wound therapy and gene therapy. However, application of exogenous single cytokine gene may not be sufficient for severe wound problems. Owing to the self renewal and multipotent characteristics of stem cells, stem cells may have the potential to differentiate into some of the essential cells in wound healing such as macrophages, keratinocytes and fibroblasts. We develop a strategy to topically apply three different types of stem cells individually with the thermosensitive hydrogel in an attempt to improve wound repair. Three new strategies in this thesis project are reported. (1) Intradermal injection of TGFƒÒ-1 plasmid DNA followed by electroporation or (2) Topical application of TGFƒÒ-1 plasmid DNA with themosensitive hydrogel made of PEG-PLGA-PEG triblock copolymer. (3) Topically application of the thermosensitive hydrogel with three different types of stem cells: muscle derived stem cell, meschenymal stem cells or heamotopoietic stem cells.
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