RGD Collagen for Engineering a Contractile Tissue and Cell Therapy after Myocardial Infarct

Currently, the clinical impact of cell therapy after a myocardial infarction (MI) is limited by low cell engraftment due to significant cell death, including apoptosis, in an infarcted, inflammatory, poor angiogenic environment, low cell retention and secondary migration. Cells interact with their environment through integrin mechanoreceptors that control their survival/apoptosis/differentiation/migration/proliferation. Optimizing these interactions may be a way of improving outcomes. The association of free cells with a 3D-scaffold may be a way to target their integrins. Collagen is the most abundant structural component of the extracellular matrix (ECM) and the best contractility levels are achieved with cellular preparations containing collagen, fibrin, or Matrigel (i.e. tumor extract). In the interactions between cells and ECM, 3 main proteins are recognised: collagen, laminin and RGD (Arg-Gly-Asp) peptide. The RGD plays a key role in heart development, after MI, and on cardiac cells. Cardiomyocytes secrete their own laminin on collagen. The collagen has a non-functional cryptic RGD and is thus suboptimal for interactions with associated cells. The use of a collagen functionalized with RGD may help to improve collagen biofunctionality. It may help in the delivery of paracrine cells, whether or not they are contractile, and in assisting tissue engineering a safe contractile tissue.