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PORCINE CARTILAGE TRANSPLANTS IN THE CYNOMOLGUS MONKEY: III. Transplantation of α-Galactosidase-Treated Porcine Cartilage

Stone, Kevin R.1; Ayala, Gustavo2; Goldstein, Jack3; Hurst, Rose3; Walgenbach, Ann1; Galili, Uri4,5

Experimental Transplantation

Background. Studies on transplantation of porcine meniscus and articular cartilage into monkeys are important for evaluating the possible use of such tissues in humans. In addition, such studies shed light on the chronic xenograft rejection process in primates. Transplantation of porcine cartilage into cynomolgus monkeys for 2 months results in a many-fold increase in anti-Gal activity and in a strong cellular inflammatory response of T lymphocytes and macrophages within the implants. The objective of this study was to determine whether elimination of Galα1-3Galβ1-4Gl-cNAc-R (α-gal epitopes) from the xenograft may alter the immune response and the inflammatory reaction.

Methods. Porcine meniscus and articular cartilage specimens were treated with recombinant α-galactosidase (100 U/ml), and the absence of α-gal epitopes was assessed by the binding of the monoclonal anti-Gal antibody M86. The treated cartilage specimens were transplanted into the suprapatellar pouch of cynomolgus monkeys. The immune response to cartilage was monitored in the serum and the inflammatory reaction was assessed in the xenografts, which were explanted after 2 months.

Results. Incubation with α-galactosidase resulted in complete removal ofα-gal epitopes from the cartilage. The increase in anti-Gal activity in the transplanted monkeys was marginal. However, most monkeys produced antibodies to antigens specific to porcine cartilage. The inflammatory response within the α-galactosidase-treated xenografts was much lower than in nontreated cartilage and the proportion of T lymphocytes within the cellular infiltrates was greatly reduced.

Conclusions. Treatment of cartilage xenografts with α-galactosidase successfully removes α-gal epitopes from porcine cartilage. Transplantation of the treated cartilage results in the production of only anti-porcine cartilage-specific antibodies and a reduced inflammatory response consisting primarily of macrophages infiltrating into the cartilage.

The Stone Clinic, San Francisco, California; Lindsley F. Kimball Research Institute, New York, New York; and Departments of Pathology and Microbiology/Immunology, MCP-Hahnemann School of Medicine, Allegheny University of the Health Sciences, Philadelphia, Pennsylvania

1The Stone Clinic.

2Department of Pathology, MCP-Hahnemann School of Medicine.

3Lindsley F. Kimball Research Institute.

4Department of Microbiology/Immunology, MCP-Hahnemann School of Medicine.

5Address correspondence to: Dr. Uri Galili, Department of Microbiology and Immunology, MCP-Hahnemann School of Medicine, Allegheny University of the Health Sciences, 2900 Queen Lane, Philadelphia, PA 19129.

Received 11 November 1997.

Accepted 8 January 1998.

© 1998 by Lippincott Williams & Wilkins