Degradation Products of Extracellular Matrix Affect Cell Migration and Proliferation

Department of Surgery, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15219, USA.
Tissue Engineering Part A (Impact Factor: 4.7). 03/2009; 15(3):605-14. DOI: 10.1089/ten.tea.2007.0425
Source: PubMed


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.

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    • "Previous studies revealed that the extracts from ECM-SIS have positive bioactive effects on the cellular activities of the healing ACLFs, such as increased cell proliferation [28]. Even the degradation products of an ECM (prehydrogel solution after enzyme digestion) have been shown to possess chemotactic and mitogenic effects [29]. "
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    ABSTRACT: SummaryBackground/Objective
    07/2015; 3(3):114-122. DOI:10.1016/
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    • "Indeed, the ECM represents the secreted product of the resident cells of each tissue or organ. It includes both functional and structural molecules arranged in a unique three-dimensional ultrastructure that supports the phenotype and the function of the resident cells (Reing et al., 2009, 2010). Appropriate tissue decellularization preserves not only the ECM integrity, bioactivity and spatial structure, but also the vascular, lymphatic and nervous network (Badylak et al., 2012). "
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    ABSTRACT: Effective clinical treatments for volumetric muscle loss resulting from traumatic injury or resection of a large amount of muscle mass are not available to date. Tissue engineering may represent an alternative treatment approach. Decellularization of tissues and whole organs is a recently introduced platform technology for creating scaffolding materials for tissue engineering and regenerative medicine. The muscle stem cell niche is composed of a three-dimensional architecture of fibrous proteins, proteoglycans, and glycosaminoglycans, synthesized by the resident cells that form an intricate extracellular matrix (ECM) network in equilibrium with the surrounding cells and growth factors. A consistent body of evidence indicates that ECM proteins regulate stem cell differentiation and renewal and are highly relevant to tissue engineering applications. The ECM also provides a supportive medium for blood or lymphatic vessels and for nerves. Thus, the ECM is the nature's ideal biological scaffold material. ECM-based bioscaffolds can be recellularized to create potentially functional constructs as a regenerative medicine strategy for organ replacement or tissue repopulation. This article reviews current strategies for the repair of damaged muscle using bioscaffolds obtained from animal ECM by decellularization of small intestinal submucosa (SIS), urinary bladder mucosa (UB), and skeletal muscle, and proposes some innovative approaches for the application of such strategies in the clinical setting.
    Frontiers in Physiology 06/2014; 5:218. DOI:10.3389/fphys.2014.00218 · 3.53 Impact Factor
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    • "In future, it will be mandatory to set up decellularization techniques that leave an intact ECM and to learn more about ECM biology to exploit native and bioengineered ECM molecules that allow a better recruitment of cells in vivo. The concept that ECM degradation can result in products with chemoattractive properties [153] needs to be further developed (Figure 2). "
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    ABSTRACT: Cardiovascular disease (CVD) is one of the leading causes of death in the Western world. The replacement of damaged vessels and valves has been practiced since the 1950's. Synthetic grafts, usually made of bio-inert materials, are long-lasting and mechanically relevant, but fail when it comes to "biointegration". Decellularized matrices, instead, can be considered biological grafts capable of stimulating in vivo migration and proliferation of endothelial cells (ECs), recruitment and differentiation of mural cells, finally, culminating in the formation of a biointegrated tissue. Decellularization protocols employ osmotic shock, ionic and non-ionic detergents, proteolitic digestions and DNase/RNase treatments; most of them effectively eliminate the cellular component, but show limitations in preserving the native structure of the extracellular matrix (ECM). In this review, we examine the current state of the art relative to decellularization techniques and biological performance of decellularized heart, valves and big vessels. Furthermore, we focus on the relevance of ECM components, native and resulting from decellularization, in mediating in vivo host response and determining repair and regeneration, as opposed to graft corruption.
    American Journal of Stem Cells 03/2014; 3(1):1-20.
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