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The Role of Matrix Metalloproteinases In Influencing Stem Cell Behavior and Skeletal Muscle Healing

Bellayr, Ian Heath (2011) The Role of Matrix Metalloproteinases In Influencing Stem Cell Behavior and Skeletal Muscle Healing. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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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.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Bellayr, Ian Heathihb4@pitt.eduIHB4
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairLi, Yongyongli@pitt.eduYONGLI
Committee MemberHuard, Johnnyjhuard@pitt.eduJHUARD
Committee MemberRoy, Parthapar19@pitt.eduPAR19
Committee MemberShroff, Sanjeevsshroff@pitt.eduSSHROFF
Committee MemberStrom, Stephenstrom@pitt.eduSTROM
Date: 19 September 2011
Date Type: Completion
Defense Date: 22 June 2011
Approval Date: 19 September 2011
Submission Date: 3 June 2011
Access Restriction: 5 year -- Restrict access to University of Pittsburgh for a period of 5 years.
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: Stem Cells; Differentiation; MMPs
Other ID:, etd-06032011-120450
Date Deposited: 10 Nov 2011 19:46
Last Modified: 15 Nov 2016 13:44


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