Abstract
Development of methods for gene transfer to synoviocytes was borne from the idea that gene therapy could be used to more effectively treat rheumatoid arthritis (EU) and other joint disorders (1). Current pharmaceutical modalities in use against RA have limited effectiveness because of problems related to inefficient targeting of drugs to the joint, as well as inefficacies of the drugs themselves. Drug delivery to the joint by traditional oral, iv, and intramuscular routes, depends on passive diffusion of the drug from the synovial vasculature into the joint space (2). Thus, high systemic concentrations of the drug are necessary to achieve therapeutic intra-articular drug levels; in chronic RA, perfusion of the synovium may be compromised (3), driving required systemic drug levels even higher. This is of major concern, as the pharmaceuticals used to treat this disease are associated with serious side effects. Further compounding these problems is the chronic nature of RA, which requires lifelong treatment with high dosages of these drugs.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Bandara, G., Robbins, P. D, Georgescu, H. I., Mueller, G. M, Glorioso, J. C., and Evans, C. H. (1992) Gene transfer to synoviocytes:prospects for gene treatment of arthritis. DNA Cell Biol. 11, 227–231.
Hung, G. L. and Evans, C. H. (1994) Synovium, in Knee Surgery (Fu, F. H, Harner, C. D., and Vince, K. G., eds.), Williams and Wilkins, Baltimore, MD, pp 141–154.
Stevens, C. R., Blake, D. R., Merry, P., Revel, P. A., and Levick, J. R. (1991) A comparative study by morphometry of the microvasculature in normal and rheumatoid synovium. Arthritis Rheum 36, 1508–1513.
Evans, C. H. and Robbins, P. D. (1994) Prospects for treating arthritis by gene therapy. J. Rheum. 21, 779–782.
Levick, J. R. (1981) Permeability of rheumatoid and normal human synovium to specific plasma proteins. Arthritis Rheum. 24, 1550–1560.
Wallis, W. J., Simkin, P. A., and Nelp, W. B. (1987) Protein traffic in human synovial effusions. Arthritis Rheum. 30, 57–63.
Evans, C. H. and Robbins, P. D. (1994) Gene therapy for arthritis, in Gene Therapeutics. Methods and Applications of Direct Gene Transfer (Wolff, J. A., ed.), Birkhauser, Boston, pp. 320–343.
Nita, I., Galea-Lauri, J., Georgescu, H. I., Mueller, G., Gao, X., Huang, L., Glorioso, J. C., Robbins, P. D., and Evans, C. H. (1994) Direct gene transfer to synovium. Transactions of the 40th Annual Meeting of the Orthopaedic Research Society 19, 479.
Bandara, G., Mueller, G. M., Galea-Lauri, J., Tindal, M. H., Georgescu, H. I., Suchanek, M. K., Hung, G. L., Glorioso, J. C., Robbins, P. D., and Evans, C. H. (1993) Intraarticular expression of biologically active interleukin 1-receptor-antagonist protein by ex vivo gene transfer. Proc Natl. Acad. Sci. USA 90, 10,764–10,768.
Hung, G L., Robbins, P. D., and Evans, C. H. (1994) Synovial Cell Transplantation, in Methods in Cell Transplantation (Ricordi, C., ed.), R. G. Landes, pp.227–234.
Revell, P. A. (1989) Synovial lining cells. Rheumatol Int. 9, 49–51.
Wilkinson, L. S., Pitsillides, A. A., Worrall, J. J., and Edwards, J. C. W. (1992) Light microscopic characterization of the fibroblast-like synovial intimal cell (synoviocyte). Arthritis Rheum. 35, 1179–1184.
Stevens, C. R., Mapp, P. I., and Revell, P. A. (1988) A monoclonal antibody (MAb 67) marks type B synoviocytes. Rheumatol Int. 10, 103–106.
Kinsella, T. D., Baum, J., and Ziff, M. (1970) Studies of isolated synovial lining cells of rheumatoid and non-rheumatoid synovial membranes Arthritis Rheum 13, 734–742.
Evans, C. H., Bandara, G., Mueller, G., Robbins, P. D., Glorioso, J. C., and Georgescu, H. I. (1992) Synovial cell transplants for gene transfer to joints. Transplantation Proc. 24, 2966.
Evans, C. H., Mazzocchi, R. A., Nelson, D. D., and Rubash, H. E. (1984) Experimental arthritis induced by intraarticular injection of allogeneic cartilaginous particles into rabbit knees, Arthritis Rheum. 27, 200–207.
Olson, E. J., Kang, J. D., Fu, F. H., Georgescu, H. I., Mason, C. G., and Evans, C. H. (1988) The biochemical and histological effects of artificial ligament wear particles: in vitro and in vivo studies. Am J. Sports Med. 16, 558–570.
Haynes, B. F., Hale, L. P., Patton, K. L., Martin, M. E., and McCallum, R. M. (1991) Measurement of an adhesion molecule as an indicator of inflammatory disease activity: up-regulation of the receptor for hyaluronan (CD44) in rheumatoid arthritis. Arthritis Rheum. 34, 1436–1443.
Galea-Lauri, J., Wilkinson, J. M., and Evans, C. H. (1993) Characterization of monoclonal antibodies against CD44: evidence of a role for CD44 in modulating synovial metabolism. Mol. Immunol. 30, 1383–1392.
Hung, G. L., Galea-Lauri, J., Mueller, G. M., Georgescu, H. I., Larkin, L. A., Suchanek, M. K., Tindal, M. H., Robbins, P. D., and Evans, C. H. (1994) Suppression of intra-articular responses to inerleukin-1 by transfer of the interleukin-1 receptor antagonist gene to synovium. Gene Ther. 1, 64–69.
Evans, C. H. and Robbins, P. D. (1994) The interleukin-1 receptor antagonist and its delivery by gene transfer. Receptor 4, 9–15.
Ohtani, K. and Evans, C. H. Manuscript in preparation.
Ohashi, T., Boggs, S., Robbins, P. D., Bahnson, A., Patrene, K., Wei, F. S., Wei, J F., Li, J, Lucht, L., Fei, Y., Clark, S, Kimak, M., He, H., Mowery-Rushton, P., and Barranger, J. A (1992) Efficient transfer and sustained high expression of the human glucocerebrosidase gene in mice and their functional macrophages following transplantation of bone marrow transduced by a retroviral vector. Proc. Natl. Acad. Sci. USA 89, 11,332–11,336.
Dranoff, G., Jaffee, E., Lazenby, A, Golumbek, P., Levitsky, H., Brose, K., Jackson, V., Hamada, H., Pardoll, D., and Mulligan, R. C. (1993) Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity. Proc Natl. Acad. Sci. USA 90, 3539–3543.
Price, J., Turner, D., and Cepko, C (1987) Lineage analysis in the vertebrate nervous system by retrovirus-mediated gene transfer. Proc Natl Acad. Sci. USA 84, 156–160.
Farndale, R. W., Buttle, D. J., and Barrett A. J. (1986) Improved quantitation and discrimination of sulfated glycosaminoglycans by use of methylene blue. Biochem. Biophys Acta 883, 173–177.
Sanes, J R., Rubenstein, J. L. R., and Nicolas, J. F (1986) Use of a recombinant retrovirus to study post-implantation cell lineage in mouse embryos EMBO J 5, 3133–3142.
Green, W. T., Jr. (1971) Behavior of articular chondrocytes. Clin Orthop. 75, 248–260.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1997 Humana Press Inc., Totowa, NJ
About this protocol
Cite this protocol
Kang, R., Robbins, P.D., Evans, C.H. (1997). Methods for Gene Transfer to Synovium. In: Robbins, P.D. (eds) Gene Therapy Protocols. Methods in Molecular Medicine, vol 7. Humana, Totowa, NJ. https://doi.org/10.1385/0-89603-484-4:357
Download citation
DOI: https://doi.org/10.1385/0-89603-484-4:357
Publisher Name: Humana, Totowa, NJ
Print ISBN: 978-0-89603-484-6
Online ISBN: 978-1-59259-591-4
eBook Packages: Springer Protocols