Cardiac Extracellular Matrix Modification as a Therapeutic Approach

Adv Exp Med Biol. 2018:1098:131-150. doi: 10.1007/978-3-319-97421-7_7.

Abstract

The cardiac extracellular matrix (cECM) is comprised of proteins and polysaccharides secreted by cardiac cell types, which provide structural and biochemical support to cardiovascular tissue. The roles of cECM proteins and the associated family of cell surface receptor, integrins, have been explored in vivo via the generation of knockout experimental animal models. However, the complexity of tissues makes it difficult to isolate the effects of individual cECM proteins on a particular cell process or disease state. The desire to further dissect the role of cECM has led to the development of a variety of in vitro model systems, which are now being used not only for basic studies but also for testing drug efficacy and toxicity and for generating therapeutic scaffolds. These systems began with 2D coatings of cECM derived from tissue and have developed to include recombinant ECM proteins, ECM fragments, and ECM mimics. Most recently 3D model systems have emerged, made possible by several developing technologies including, and most notably, 3D bioprinting. This chapter will attempt to track the evolution of our understanding of the relationship between cECM and cell behavior from in vivo model to in vitro control systems. We end the chapter with a summary of how basic studies such as these have informed the use of cECM as a direct therapy.

Keywords: Bioink; Bioprinting; Cardiac repair; Cardiac therapy; ECM mimetic; Recombinant ECM.

Publication types

  • Review

MeSH terms

  • Animals
  • Biopolymers / chemistry
  • Cell Growth Processes
  • Cell Transplantation / methods
  • Drug Evaluation, Preclinical / methods
  • Extracellular Matrix Proteins / deficiency
  • Extracellular Matrix Proteins / physiology
  • Extracellular Matrix Proteins / therapeutic use
  • Extracellular Matrix* / chemistry
  • Extracellular Matrix* / physiology
  • Extracellular Matrix* / ultrastructure
  • Humans
  • In Vitro Techniques
  • Mice
  • Mice, Knockout
  • Myocardium / ultrastructure*
  • Myocytes, Cardiac / cytology
  • Printing, Three-Dimensional
  • Recombinant Proteins / therapeutic use
  • Regenerative Medicine / methods*
  • Tissue Engineering / methods*
  • Tissue Scaffolds*

Substances

  • Biopolymers
  • Extracellular Matrix Proteins
  • Recombinant Proteins