Injection into the heart tissue is a direct route for optimally placing mesenchymal stem cells (MSC) to regulate local inflammation following a heart attack. The retention of MSCs at the injection site is severely limited by the fluid flows that rapidly wash cells away and minimize their capacity to modulate cardiac inflammation. To prevent this loss of MSCs and their function, antibody coatings were designed for the surface of MSCs to enhance their adhesion to the inflamed tissue. MSCs were biotinylated, and biotinylated antibodies against intercellular cell adhesion molecules were conjugated to the cell surface through an intermediate layer of streptavidin. MSC surfaces were modified with ~7,000 biotin/μm2 and ~23 antibodies/μm2. The heart tissue injection of antibody-coated MSCs offered a 3-fold increase of cell retention in an infarcted heart over the injection of uncoated MSCs. We supported the mechanism of adhesion through analysis of MSC adhesion to inflamed endothelial cells and also surfaces of purified adhesion molecules on glass under microfluidic shear flow.
Keywords: Cell surface coating; ICAM1 antibody; endothelium targeting; intramyocardial delivery; targeted cell delivery.