Effect of the alphaGal epitope on the response to small intestinal submucosa extracellular matrix in a nonhuman primate model.
The Galalpha1,3Galbeta1,4GlcNAc-R (Gal) epitope is a major factor in the hyperacute rejection of pig organ transplants in primates. Biologic scaffold materials used for tissue reconstruction and composed of xenogeneic extracellular matrix (ECM) may contain the Gal epitope. However, the effect of this epitope upon the host response is controversial. The present study investigated the effect of the Gal epitope upon the host response to a porcine-derived ECM in an African Green monkey (Cholrocaebus aethiops) abdominal wall resection model. Histologic methods, serology, complement-dependent cytotoxicity, and gene expression profiling were used to evaluate the host response to allogeneic and both wild-type and Gal-deficient xenogeneic scaffold materials. Although expression of the Gal epitope induced an increase in serum anti-Gal antibodies in recipients, no other differences were noted in the host response between test articles. All ECM scaffolds were well tolerated and showed constructive remodeling during the study period. Recipients of all test articles showed no histologic or humoral evidence of sensitization when a second scaffold was implanted 45 days after the original surgery. The findings of the present study show that the presence of the Gal epitope within a porcine-derived ECM scaffold material elicits a serum antibody response, but no adverse effect upon tissue remodeling.
Daly
Kerry A
KA
Department of Surgery, McGowan Institute of Regenerative Medicine, University of Pittsburgh, Pennsylvania 15219, USA.
Stewart-Akers
Ann M
AM
Hara
Hidetaka
H
Ezzelarab
Mohamed
M
Long
Cassandra
C
Cordero
Kevin
K
Johnson
Scott A
SA
Ayares
David
D
Cooper
David K C
DK
Badylak
Stephen F
SF
D000818:Animals; D000906:Antibodies / Q000097:blood; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D005109:Extracellular Matrix / Q000276:immunology*; D005453:Fluorescence; D005786:Gene Expression Regulation; D006801:Humans; D020007:Implants, Experimental; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology* / Q000601:surgery; D007421:Intestine, Small / Q000166:cytology / Q000276:immunology* / Q000601:surgery; D011323:Primates / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D034421:Sus scrofa; D014183:Transplantation, Heterologous; D014184:Transplantation, Homologous; D014312:Trisaccharides / Q000276:immunology*
D000906:Antibodies; D014312:Trisaccharides; C076569:alpha-galactosyl epitope