Stem cells are highly valued for their capacity to aid in the functional recovery of damaged or diseased tissue. They are defined by their remarkable ability to maintain their undifferentiated state through countless cycles of cell division and to differentiate into variable types of specialized cells. Since ethical controversy has hindered funding for embryonic stem cell research and induced pluripotent stem cells are in the initial stages of investigations, much research has been conducted using adult stem cells. The use of adult stem cells in clinical applications is gradually becoming a reality; however, the major limitation is the difficulty to isolate, purify and expand them in culture.
Matrix metalloproteinases (MMPs) have been regarded as a group of zinc-endopeptidases that influence tissue remodeling by degrading constituents of the extracellular matrix to actively promote cell proliferation, migration, apoptosis and differentiation. They have been suggested to play important roles in the regeneration of amputated newt limbs by contributing to a population of undifferentiated stem cells, called a blastema, which is likely formed by cell dedifferentiation.
The research presented here builds on previous work investigating the therapeutic use of MMP1. Investigations have demonstrated the ability of MMP1 to aid in the recovery of skeletal muscle tissue by degrading fibrous scar tissue to facilitate cell migration and differentiation. This work examines the potential of MMP1 in skeletal muscle healing to stimulate stem cell behavior by the expression of certain muscle stem cell markers and its impact on cell differentiation. In addition, stem cells derived from skeletal muscle tissue were investigated to thoroughly elucidate the effect of blocking MMP signaling. MMP inhibition using GM6001 was observed to negatively impact muscle stem cell migration, stem cell associated markers and their differentiation capacity thus indicating the key role of MMPs in muscle stem cell behavior.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-06032011-120450 |
| Date | 19 September 2011 |
| Creators | Bellayr, Ian Heath |
| Contributors | Johnny Huard, Partha Roy, Sanjeev Shroff, Yong Li, Stephen Strom |
| 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-06032011-120450/ |
| 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. |
Page generated in 0.0014 seconds