Effect of the αGal Epitope on the Response to Small Intestinal Submucosa Extracellular Matrix in a Nonhuman Primate Model

被引:0
|
作者
Daly, Kerry A. [1 ]
Stewart-Akers, Ann M. [1 ]
Hara, Hidetaka [2 ]
Ezzelarab, Mohamed [2 ]
Long, Cassandra [2 ]
Cordero, Kevin [1 ]
Johnson, Scott A. [1 ]
Ayares, David [3 ]
Cooper, David K. C. [2 ]
Badylak, Stephen F. [1 ]
机构
[1] Univ Pittsburgh, McGowan Inst Regenerat Med, Dept Surg, Pittsburgh, PA 15219 USA
[2] Univ Pittsburgh, Med Ctr, Thomas E Starzl Transplantat Inst, Pittsburgh, PA 15219 USA
[3] Revivicor Inc, Blacksburg, VA USA
关键词
GENE-KNOCKOUT PIGS; ALPHA-1,3-GALACTOSYLTRANSFERASE GENE; IMMUNE-RESPONSE; XENOGRAFT REJECTION; CARDIAC XENOGRAFTS; HUMORAL REJECTION; PORCINE; ANTIBODIES; BABOONS; SCAFFOLD;
D O I
10.1089/ten.tea.2009.0089
中图分类号
Q813 [细胞工程];
学科分类号
摘要
The Gal alpha 1,3Gal beta 1,4GlcNAc-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.
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收藏
页码:3877 / 3888
页数:12
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