title: Matrix-specific anchors: a new concept for targeted delivery and retention of therapeutic cells.
abstract: Biomedical strategies for tissue engineering and repair utilize specific cells, scaffolds, and growth factors to reconstruct elements of damaged tissue. The cellular element of these strategies is limited, however, by poor efficiency of delivery and retention of therapeutic cells in target sites. We propose that the presence of a cellular anchor that is 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 do so, we engineered an artificial collagen-specific anchor (ACSA) that is 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 that recognizes a unique epitope present in human collagen I. Meanwhile, 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 interacted with its intended target, that is, collagen I. We have demonstrated that, in comparison to the control, the cells expressing the ACSA attached better to collagen I and exhibited improved retention in sites of seeding. 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, the findings described here could have a broad positive impact for 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 fibronectins.
authors.affiliation: 1 Division of Orthopaedic Research, Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University , Philadelphia, Pennsylvania.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Steplewski
authors.forename: Jolanta
authors.initials: J
authors.lastname: Fertala
authors.forename: Pedro
authors.initials: P
authors.lastname: Beredjiklian
authors.forename: Mark L
authors.initials: ML
authors.lastname: Wang
authors.forename: Andrzej
authors.initials: A
authors.lastname: Fertala
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects; D002450:Cell Communication / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D024042:Collagen Type I / Q000494:pharmacology; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D005782:Gels / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D015398:Signal Transduction / Q000187:drug effects; D033581:Stem Cell Transplantation; D023822:Tissue Engineering / Q000379:methods*; D014161:Transduction, Genetic
chemical_list: D024042:Collagen Type I; D005782:Gels; D049452:Green Fluorescent Proteins