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DEVELOPING TISSUE ENGINEERING AND GENE THERAPY APPROACHES INVOLVING THE USE OF NERVE GROWTH FACTOR AND MUSCLE-DERIVED STEM CELLS TO IMPROVE THE REGENERATION OF DYSTROPHIC MUSCLE

Lavasani, Mitra (2005) DEVELOPING TISSUE ENGINEERING AND GENE THERAPY APPROACHES INVOLVING THE USE OF NERVE GROWTH FACTOR AND MUSCLE-DERIVED STEM CELLS TO IMPROVE THE REGENERATION OF DYSTROPHIC MUSCLE. Master's Thesis, University of Pittsburgh. (Unpublished)

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Abstract

In recent years, researchers have attempted to use gene- and cell-based therapies to restore dystrophin and alleviate the muscle weakness that results from Duchenne muscular dystrophy (DMD). Our research group has isolated a population of muscle-derived stem cells (MDSCs) from the postnatal skeletal muscle of mice. In comparison with satellite cells, MDSCs display an improved transplantation capacity in dystrophic mdx muscle that can be attributed to their ability to undergo long-term proliferation, self-renewal, and multipotent differentiation, including differentiation toward endothelial and neuronal lineages. The overall goal of this study was to investigate whether the use of nerve growth factor (NGF) improves the transplantation efficiency of MDSCs. Two methods of in vitro NGF stimulation were used: retroviral transduction of MDSCs with a CLNGF vector to constitutively express NGF and direct stimulation of MDSCs with NGF protein. Neither method of NGF treatment changed the marker profile or proliferation behavior of the MDSCs, but direct stimulation with NGF protein significantly delayed cells' in vitro differentiation ability. Stimulation with NGF also significantly enhanced the engraftment efficiency of MDSCs transplanted within the dystrophic muscle of mdx mice, resulting in better muscle regeneration. These findings highlight the importance of NGF as a modulatory molecule, the study of which will broaden our understanding of its biological role in the regeneration and repair of skeletal muscle by muscle-derived cells.

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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Lavasani, Mitramil39@pitt.eduMIL39
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairHuard, Johnnyjhuard@pitt.eduJHUARD
Committee MemberBorovetz, Harvey Sborovetzhs@msx.upmc.edu
Committee MemberPéault, Brunobmp13@pitt.eduBMP13
Committee MemberXiao, Xiaoxiaox@pitt.eduXIAOX
Date: 13 October 2005
Date Type: Completion
Defense Date: 30 June 2005
Approval Date: 13 October 2005
Submission Date: 18 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: MSBeng - Master of Science in Bioengineering
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: Gene Therapy; Muscle-Derived Stem Cells; Muscle Dystrophy; Muscle Regeneration; Cell Transplantation; Nerve Growth Factor
Other ID: http://etd.library.pitt.edu/ETD/available/etd-07182005-133523/, etd-07182005-133523
Date Deposited: 10 Nov 2011 19:51
Last Modified: 15 Nov 2016 13:46
URI: http://d-scholarship.pitt.edu/id/eprint/8424

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