Peripheral nerve injuries are frequently encountered in trauma, sports accidents, military activities, and degenerative muscle diseases. Like most neurological conditions, patients exhibit pain, sensory and motor deficits, and functional disability. Despite all the advances in biomedical science and technology, achieving full function and organ reinnervation after these injuries remains a major challenge. High costs of healthcare, loss of employment, and social disruption have provided the impetus for active research focusing on improved strategies for repair and regeneration. Stem cell therapy holds tremendous potential for the treatment of pathologic conditions and has consequently emerged as a new area of focus in regenerative medicine. Stem cells isolated from skeletal muscle have been shown to be both pluripotent and of significant therapeutic value; however, their ability to undergo neurogenic differentiation has yet to be investigated. Here, we report that progenitor cells isolated from skeletal muscles of both mouse and human, using our established preplate technique, adopt neuronal and glial phenotypes under controlled culture conditions. Transplantation of these cells into a critical-size sciatic nerve defect allowed full nerve restoration with induction of axonal regeneration through myelin-producing Schwann-like cells. Functional recovery resulted in improved gait of cell-transplanted mice.
Multi-lineage progenitor cells have been recently identified in blood vessel walls, notably in skeletal muscle, and venous grafts have been used effectively to bridge nerve defects experimentally and clinically, through unknown cellular mechanisms. In a sex-mismatch model, we identified donor-derived Y chromosomes co-localized with host Schwann cells nuclei, indicating nerve repair through vein grafting are mediated by vascular cells. A sustained decrease in nerve regeneration by decellularized or irradiated venous grafts also highlights the contribution of blood vessel-derived cells to nerve repair. Together, these findings not only identify the cellular basis for the efficacy of therapeutic vein wrapping, but also reinforce the emerging view of muscle cell-mediated therapy for peripheral neuropathies.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-11192008-113051 |
| Date | 30 June 2011 |
| Creators | Lavasani, Mitra |
| Contributors | Johnny Huard, Robert J. Goitz, Kacey G. Marra, Bruno Peault, Jonathan B. Pollett |
| 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-11192008-113051/ |
| Rights | restricted, 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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