Degradation Products of Extracellular Matrix Affect Cell Migration and Proliferation

TLDR

Extracellular matrix scaffolds are widely used in regenerative medicine, yet the host remodeling response is incompletely understood, with recent evidence indicating that both growth factors and biologically active degradation products contribute to tissue repair. This study aimed to assess whether physiologically relevant in vitro degradation of ECM scaffolds generates products that are chemotactic and/or mitogenic for differentiated endothelial cells and undifferentiated progenitor cells. Porcine urinary bladder ECM was enzymatically degraded with pepsin/HCl or papain, and the resulting fragments were evaluated for chemotaxis using 48‑well filter chambers or fluorescence assays and for mitogenicity in proliferation assays. The degradation products stimulated chemotaxis and proliferation of multipotential progenitor cells while simultaneously inhibiting chemotaxis and proliferation of differentiated endothelial cells, underscoring their role as modulators of cell recruitment and proliferation during scaffold remodeling.

Abstract

Biologic scaffolds composed of extracellular matrix (ECM) are utilized in numerous regenerative medicine applications to facilitate the constructive remodeling of tissues and organs. The mechanisms by which the host remodeling response occurs are not fully understood, but recent studies suggest that both constituent growth factors and biologically active degradation products derived from ECM play important roles. The objective of the present study was to determine if degradation of ECM scaffold materials in vitro by methods that are biochemically and physiologically relevant can yield products that possess chemotactic and/or mitogenic activities for fully differentiated mammalian endothelial cells and undifferentiated multipotential progenitor cells. ECM harvested from porcine urinary bladder was degraded enzymatically with pepsin/hydrochloric acid or papain. The ECM degradation products were tested for chemoattractant properties utilizing either 48-well chemotaxis filter migration microchambers or fluorescence-based filter migration assays, and were tested for mitogenic properties in cell proliferation assays. Results showed that ECM degradation products possessed chemotactic and mitogenic activities for multipotential progenitor cells and that the same degradation products inhibited both chemotaxis and proliferation of differentiated endothelial cells. These findings support the concept that degradation products of ECM bioscaffolds are important modulators of the recruitment and proliferation of appropriate cell types during the process of ECM scaffold remodeling.