Effects of reduction in the alpha‐gal antigen on bony union: a model of xenobone graft using GalT knockout mouse. (17th March 2014)

• Record Type: Journal Article
• Authors: Park, Moon Seok; Kim, Tae Gyun; Lee, Kyoung Min; Chung, Chin Youb; Kwon, Soon‐Sun; Yoon, Il‐Hee; Park, Chung‐Gyu
• Is Part Of: Xenotransplantation. Volume 21:Number 3(2014:May/Jun.)
• Page Start: 267
• Page End: 273
• Publication Date: 2014-03-17
• Subjects: Xenografts -- Periodicals; Transplantation of organs, tissues, etc -- Periodicals; 617.95
• DOI: 10.1111/xen.12092
• Languages: English
• ISSNs: 0908-665X

Abstract

<abstract abstract-type="main" id="xen12092-abs-0001"> <title>Abstract</title> <sec id="xen12092-sec-0001" sec-type="section"> <title>Background</title> <p>Among the bone graft sources used currently, the availability of autografts is limited and allografts are expensive. Therefore, xenobone grafts have drawn attention as a new source of bone grafts, although immunologic rejection issues are unresolved. This study used a GalT knockout mouse model to investigate the effects of reducing the alpha‐gal epitope using alpha‐galactosidase on the union of porcine xenobone grafts.</p> </sec> <sec id="xen12092-sec-0002" sec-type="section"> <title>Methods</title> <p>Sixty‐eight alpha‐gal knockout C57/BL6 mice and eight wild‐type mice were used. The mice were divided into five groups: In group 1 (26 alpha‐gal knockout mice), an alpha‐galactosidase‐treated porcine xenograft was transplanted into the mouse femur to reduce antigenicity, and intramedullary fixation was performed. In group 2 (26 alpha‐gal knockout mice), a non‐treated porcine xenobone graft was performed. In group 3 (eight alpha‐gal knockout C57/BL6 mice), syngenic bone grafts were performed. In group 4 (eight wild‐type C57/BL6 mice), syngenic bone grafts were performed. In group 5 (eight C57/BL6 alpha‐gal knockout mice), a bone defect model was obtained by maintaining the gap of the osteotomy site. Groups 3, 4, and 5 were used for positive and negative control groups. Qualitative immunohistochemical analysis of the porcine bone was performed to detect the presence of the alpha‐gal epitope in groups 1 and 2. The concentration of the anti‐alpha‐gal antibody was evaluated using a quantitative enzyme‐linked immunosorbent assay (ELISA) at the time of sacrifice (3, 4, and 5 weeks after the operation). Histologic and radiologic results (Goldberg method) for the bone union were compared.</p> </sec> <sec id="xen12092-sec-0003" sec-type="section"> <title>Results</title> <p>The qualitative immunohistochemical analysis showed that the alpha‐gal epitope was reduced when xenobone grafts were treated with alpha‐galactosidase. Compared with group 2, group 1 showed a low anti‐alpha‐gal antibody concentration in the ELISA results. In group 2, the anti‐alpha‐gal antibody concentration increased with time. Group 1 showed significantly better histologic union than group 2, but the amount of radiologic union was similar in the two groups.</p> </sec> <sec id="xen12092-sec-0004" sec-type="section"> <title>Conclusions</title> <p>Alpha‐galactosidase treatment of a porcine xenobone graft can reduce the alpha‐gal epitope. This reduction in the antigen could significantly reduce the humoral immune response to the alpha‐gal antigen in C57/BL6 alpha‐gal knockout mice, leading to significant improvements in histologic union. This study provides a relevant GalT knockout mouse model for detecting the effects of alpha‐gal epitope reduction by alpha‐galactosidase on the union of porcine xenobone grafts.</p> </sec> </abstract>