Porcine cartilage transplants in the cynomolgus monkey. III. Transplantation of alpha-galactosidase-treated porcine cartilage.
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 Galalpha1-3Galbeta1-4GlcNAc-R (alpha-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 alpha-galactosidase (100 U/ml), and the absence of alpha-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 alpha-galactosidase resulted in complete removal of alpha-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 alpha-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 alpha-galactosidase successfully removes alpha-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, USA.
K R
KR
Stone
G
G
Ayala
J
J
Goldstein
R
R
Hurst
A
A
Walgenbach
U
U
Galili
D000818:Animals; D002356:Cartilage / Q000276:immunology / Q000637:transplantation*; D008252:Macaca fascicularis; D013552:Swine; D014183:Transplantation, Heterologous / Q000276:immunology*; D014312:Trisaccharides / Q000032:analysis; D000519:alpha-Galactosidase / Q000494:pharmacology*
D014312:Trisaccharides; C076569:alpha-galactosyl epitope; D000519:alpha-Galactosidase