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Recruitment of Progenitor Cell Populations by Chemoattractant Degradation Products of Extracellular Matrix Scaffolds

Brennan, Ellen Patricia (2010) Recruitment of Progenitor Cell Populations by Chemoattractant Degradation Products of Extracellular Matrix Scaffolds. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Biologic scaffolds composed of extracellular matrix (ECM) have been successfully used as templates for the constructive remodeling of numerous tissues in preclinical studies and human clinical applications. The mechanisms by which ECM induces remodeling are largely unknown, but the degradation products of ECM may play key roles in constructive remodeling. This dissertation investigated the hypothesis that ECM degradation products possess chemoattractant properties for progenitor cell (PC) populations that participate in constructive remodeling. We investigated different methods of in vitro degradation of ECM and determined physiologically relevant methods of degradation yielded degradation products with chemoattractant activity. Both pepsin and collagenase digestion of ECM resulted in chemoattraction of two distinct PC populations. We then investigated if ECM degradation products from a given tissue have more potent chemoattractant properties for PCs derived from the same tissue type than for PCs derived from other tissues. Although ECM derived from skin, liver, small intestine, and urinary bladder were all chemoattractive for at least one PC population, a tissue-specific chemotactic effect was not observed in studies using skin, liver, and intestinal PCs. However, results showed that the age and species from which ECM is harvested has an effect on the chemoattractant potential of the ECM for some PC populations. We investigated if prevention or retardation of ECM degradation in vivo would reduce bone marrow-derived PC involvement in constructive remodeling, yielding a different histomorphologic outcome than normal ECM degradation. Bone marrow-derived cells (BMCs) participated in the early remodeling of wounded mouse skin treated with rapidly degrading ECM scaffolds. By 28 days post-surgery, the number of BMCs returned to normal levels, suggesting that these cells do not participate in long-term constructive remodeling of mouse skin. Slowly degrading chemically crosslinked ECM scaffolds did not recruit more BMCs than are found in normal uninjured mouse skin at any time investigated. Wounds treated with rapidly degrading ECM appeared to remodel more rapidly than other treatment groups. These results suggest that scaffold type affects the temporal remodeling of injured mouse skin and that while BMCs participate in remodeling of skin wounds in mice, local tissue cells may also play an important role.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Brennan, Ellen
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairBadylak, Stephenbadylaks@upmc.eduSFB8
Committee MemberLagasse,
Committee MemberMarra, Kaceymarrkx@UPMC.EDU
Committee MemberRoy, Parthaproy@engr.pitt.eduPAR19
Date: 26 January 2010
Date Type: Completion
Defense Date: 17 August 2009
Approval Date: 26 January 2010
Submission Date: 20 August 2009
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
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: biomaterials; chemotaxis; extracellular matrix
Other ID:, etd-08202009-140247
Date Deposited: 10 Nov 2011 20:00
Last Modified: 19 Dec 2016 14:37


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