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.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-07182005-133523 |
| Date | 13 October 2005 |
| Creators | Lavasani, Mitra |
| Contributors | Dr. Harvey S. Borovetz, Dr. Johnny Huard, Dr. Bruno Péault, Dr. Xiao Xiao |
| Publisher | University of Pittsburgh |
| Source Sets | University of Pittsburgh |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf, video/x-msvideo |
| Source | http://etd.library.pitt.edu/ETD/available/etd-07182005-133523/ |
| 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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