(Taken from the application): There is now a substantive body of literature documenting the critical role the menisci play in the general biomedical functioning of the knee joint and the specific protection of articular cartilage. The data in the literature supporting a casual relationship between tears and meniscus and damage to the articular cartilage is persuasive. Moreover, it would appear that the effectiveness of an chondroprotective regimen for articular cartilage in the joint would very probably have a limited chance of success in the presence of a defective meniscus. The capability of the meniscus to heal tears would be greatly increased if the time interval it took to populate the defect with repairing cells could be shortened. The hypothesis is here advanced that the insertion of exogenous haptotactic factors into the defect will hasten recruitment of cells and provide a facilitating environment for assembly of a matrix within the defect. In in vitro studies we demonstrate that purified type VI collagen, a cell-matrix connecting protein, is a potent haptotactic agent for isolated meniscal cells in Boyden. We shall generate 2 mm diameter defects in canine medial menisci in vitro and fill these defects with a fibrin gel containing type VI collagen with/without additives. In a secondary series of experiments, the fibrin gel will be mixed with a ternary complex composed of type VI collagen bound to heparin which is in turn bound to IGF-2 (bFGF). Holes with just fibrin alone or with no additive will serve as negative controls. The menisci will be maintained in organ culture for varying lengths of time. After harvesting, the tissue with the plug will be assessed morphologically for migration of cells into the wound site. Immunolocalization experiments with antibodies against type II collagen, type VI collagen, and type I collagen will determine the quality of the new matrix made. RNAse protection assays for COL1 and COL2 gene expression will determine the Phenotypic state of the cells and whether an intermediary chondroid state precedes the emergence of a mature meniscal cell in these wounds. These studies will determine whether exogenous haptotactic factors promote cell recruitment and matrix synthesis to and within meniscal wounds in vitro.
| Kambic, Helen E; McDevitt, Cahir A (2005) Spatial organization of types I and II collagen in the canine meniscus. J Orthop Res 23:142-9 |
| Valiyaveettil, Manojkumar; Mort, John S; McDevitt, Cahir A (2005) The concentration, gene expression, and spatial distribution of aggrecan in canine articular cartilage, meniscus, and anterior and posterior cruciate ligaments: a new molecular distinction between hyaline cartilage and fibrocartilage in the knee joint. Connect Tissue Res 46:83-91 |
