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-Ò1 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-Ò1 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 TGFÒ-1 plasmid DNA followed by electroporation or (2) Topical application of TGFÒ-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.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-07242005-181117 |
| Date | 14 October 2005 |
| Creators | Lee, Pui-yan R |
| Contributors | Kacey Marra, Leaf Huang, Patricia Hebda, Johnny Huard |
| Publisher | University of Pittsburgh |
| Source Sets | University of Pittsburgh |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.pitt.edu/ETD/available/etd-07242005-181117/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Pittsburgh or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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