PORCINE CARTILAGE TRANSPLANTS IN THE CYNOMOLGUS MONKEY - III - TRANSPLANTATION OF ALPHA-GALACTOSIDASE-TREATED PORCINE CARTILAGE

Background. Studies on transplantation of porcine meniscus and articul ar cartilage into monkeys are important for evaluating the possible us e of such tissues in humans. In addition, such studies shed light on t he chronic xenograft rejection process in primates. Transplantation of porcine cartilage into cynomolgus monkeys for 2 months results in a m any-fold increase in anti-Gal activity and in a strong cellular inflam matory response of T lymphocytes and macrophages within the implants. The objective of this study was to determine whether elimination of Ga l alpha 1-3Gal beta 1-4Gl-cNAc-R (alpha-gal epitopes) from the xenogra ft may alter the immune response and the inflammatory reaction. Method s. Porcine meniscus and articular cartilage specimens were treated wit h recombinant alpha-galactosidase (100 U/ml), and the absence of alpha -gal epitopes was assessed by the binding of the monoclonal anti-Gal a ntibody M86. The treated cartilage specimens were transplanted into th e suprapatellar pouch of cynomolgus monkeys. The immune response to ca rtilage was monitored in the serum and the inflammatory reaction was a ssessed in the xenografts, which were ex-planted after 2 months. Resul ts. Incubation with alpha-galactosidase resulted in complete removal o f cu-gal epitopes from the cartilage. The increase in anti-Gal activit y in the transplanted monkeys was marginal. However, most monkeys prod uced antibodies to antigens specific to porcine cartilage. The inflamm atory response within the alpha-galactosidase-treated xenografts was m uch lower than in nontreated cartilage and the proportion of T lymphoc ytes within the cellular infiltrates was greatly reduced. Conclusions. Treatment of cartilage xenografts with alpha-galactosidase successful ly removes alpha-gall epitopes from porcine cartilage. Transplantation of the treated cartilage results in the production of only anti-porci ne cartilage-specific antibodies and a reduced inflammatory response c onsisting primarily of macrophages infiltrating into the cartilage.