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Cell/Gene Therapy For Diabetic Wound Healing

Lee, Pui-yan R (2005) Cell/Gene Therapy For Diabetic Wound Healing. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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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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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Lee, Pui-yan Rprlst4@pitt.eduPRLST4
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairHuang, Leafleafh@pitt.eduLEAFH
Committee MemberHuard, Johnnyjhuard@pitt.eduJHUARD
Committee MemberMarra, Kaceykgm5@pitt.eduKGM5
Committee MemberHebda,
Date: 14 October 2005
Date Type: Completion
Defense Date: 20 July 2005
Approval Date: 14 October 2005
Submission Date: 24 July 2005
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Institution: University of Pittsburgh
Schools and Programs: Swanson School of Engineering > Bioengineering
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: Diabetic Wound Healing; Electroporation; Naked DNA; Stem cells; Thermosensitive Hydrogel
Other ID:, etd-07242005-181117
Date Deposited: 10 Nov 2011 19:53
Last Modified: 15 Nov 2016 13:46


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