Matrix-Specific Anchors: A New Concept for Targeted Delivery and Retention of Therapeutic Cells.

Biomedical strategies for tissue engineering and repair utilize specific cells, scaffolds, and growth factors whose role is to reconstruct elements of damaged tissue. One of the limitations associated with the cellular element of these strategies is poor efficiency of delivery and retention of therapeutic cells in target sites. To circumvent this problem, here, we explored the possibility of improving the retention of cells in target sites by employing a site-specific anchor expressed on surfaces of therapeutic cells. We propose that the presence of such an anchor able to specifically bind a defined element of target tissue will facilitate efficient binding and retention of therapeutic cells, thereby promoting repair of the target site. To test this concept, we engineered artificial collagen specific anchor (ACSA) able to specifically bind collagen I. The ACSA was engineered by creating a construct comprising rationally designed consecutive domains; the binding specificity of the ACSA was achieved by employing variable regions of a monoclonal antibody recognizing a unique epitope present in human collagen I, while cell membrane localization of the ACSA was provided by the presence of a transmembrane domain. We determined that the ACSA was localized within cell membranes and was able to interact with its intended target, i.e. collagen I. We have demonstrated that, in comparison to the control, the cells expressing the ACSA were characterized by superior attachment to collagen I and their retention in sites of seeding was greatly improved. We have also demonstrated that the presence of the ACSA did not interfere with cell proliferation, the biosynthesis of endogenous collagen I, or the biological functions of native collagen receptors. Since the presented cell-delivery system utilizes a common characteristic of major connective tissues, namely the presence of collagen I, we postulate that the studies described here will have a broad positive impact on improving the repair processes of tendon, ligament, bone, intervertebral disc, skin, and other collagen I-rich connective tissues. If successful, the ACSA approach to deliver cells will serve as an outline for developing cell-delivery methods that target other elements of extracellular matrices, including other collagen types, laminins, and fibronectin.