Cardiovascular Repair: Scaffold addition of engineered macrophages to create a healing tissue engineering construct

It has been estimated that cardiovascular disease and subsequent heart attacks have claimed about 17.1 million lives worldwide in 2010 alone and as such, is an important target for new therapeutic developments. A major problem following a myocardial infarction is the resultant non-regenerative dead cardiac tissue caused by coronary artery blockage. Regenerative technologies and treatments for this condition are necessary to regrow heart tissue in these necrotic regions, in order to restore or improve heart function. Implantation of functional cardiac cells has been a proposed therapy to damaged heart tissue after myocardial infarction; however this method only replaces existing dead cells and lacks control of the healing process. We propose an additive component to this therapy, in which engineered macrophages (MΦ) are added to the cardiac cell scaffolds in order to facilitate cardiac tissue regeneration by controlling both the inflammatory and host response. An inducible M2 MΦ cell has been created and an inducible M1 MΦ construct is being made through protein engineering techniques utilizing the chemically induced dimerization (CID) system. MΦs can be polarized in vitro to a M1 phenotype or a M2 phenotype by a specific ligand and subsequent dimerization of a particular receptor. This CID system allows for receptor dimerization and activation of these specific receptor pathways in the absence of their specific ligands. To test for the polarization of engineered MΦs into a M1 or M2 MΦ phenotype through the induced activation of the TLR4 or IL4R pathway, respectively, key cell markers are being measured.