Grants We Funded

Abstract
Normal cartilage is immunologically privileged by virtue of the absence of blood and lymphatic vessels. Chondrocytes that are embedded in lacunae within the extracellular matrix obtain nutrients through diffusion from the synovial fluid in the joint cavity but are excluded from interacting with cells of the immune system by their protective extracellular matrix. Under pathologic conditions, cartilage cells are exposed and can interact with lymphocytes and other cells present in the synovial tissue and fluid. For example, human articular cartilage chondrocytes from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) express class II major histocompatibility (MHC) antigens, a potent activator of immune cells. These antigens are not known to be expressed in the absence of pathology, and their presence in RA/OA may underlie an immune response to exposed chondrocytes in these conditions. As the potential for tissue engineering approaches expands for cartilage repair, chondrocytes can be transplanted across syngeneic, allogeneic and xenogeneic barriers. During the process of engineering cartilage, chondrocytes are removed from their native immunoprotective matrix and the cell surface antigens are exposed to immunologic or antigen-presenting cells. This may lead to immune reaction against the naked chondrocytes, which may lead to pathologic conditions like those associated with arthritis. However, little is known about the expression of MHC molecules (class I or II) in engineered cartilage and their propensity to stimulate an immune response by the host. Our laboratory has extensive experience in the field of tissue engineering cartilage using swine chondrocytes obtained from various anatomical sites (e.g. articular joints, ribs, ears, etc.) and encapsulated in biological or synthetic hydrogels. The Transplantation Biology Research Center (TBRC) of the Massachusetts General Hospital has developed a unique population of swine in which the immunogenetics have been mapped in order to perform well-controlled organ and tissue transplantation studies in a large animals. We propose to use these swine and the numerous cell-marker antibodies available to study the immunogenicity of chondrocytes in large animals that will serve as a valuable preclinical cartilage repair model.