Recruitment of progenitor cell populations by chemoattractant degradation products of extracellular matrix scaffolds
Year: 2009
Type: article
Abstract: 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.
Author: Ellen P. Brennan
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2143076490