Repair of bone defects in rhesus monkeys with alpha 1,3-galactosyltransferase-knockout pig cancellous bone
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Date
2022
Authors
Wang, W.
Lu, J.
Song, Y.
Zeng, C.
Wang, Y.
Yang, C.
Huang, B.
Dai, Y.
Yang, J.
Lai, L.
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Frontiers in Bioengineering and Biotechnology, 2022; 10(990769):1-13
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Introduction: Since xenografts offer a wide range of incomparable advantages, they can be a better option than allografts but only if the possibility of immunological rejection can be eliminated. In this study, we investigated the ability of alpha 1,3-galactosyltransferase (alpha 1,3-GT) gene knockout (GTKO) pig cancellous bone to promote the repair of a femoral condyle bone defect and its influence on heterologous immune rejection. Materials and methods: Cylindrical bone defects created in a rhesus monkey model were transplanted with GTKO bone, WT bone or left empty. For immunological evaluation, T lymphocyte subsets CD4(+) and CD8(+) in peripheral blood were assayed by flow cytometry, and the IL-2 and IFN-gamma contents of peripheral blood serum were analyzed by ELISA at 2, 5, 7, 10, and 14 days post-surgery. Micro-CT scans and histological assessment were conducted at 4 and 8 weeks after implantation. Results: Compared with WT-pig bone, the heterologous immunogenicity of GTKO-pig bone was reduced. The defect filled with fresh GTKO-pig bone was tightly integrated with the graft. Histological analysis showed that GTKO-pig cancellous bone showed better osseointegration and an appropriate rate of resorption. Osteoblast phenotype progression in the GTKO group was not affected, which revealed that GTKO-pig bone could not only fill and maintain the bone defect, but also promote new bone formation. Conclusion: GTKO-pig cancellous bone decreased the ratio of CD4(+) to CD8(+) T cells and cytokines (IFN-gamma and IL-2) to inhibit xenotransplant rejection. Moreover, GTKO group increased more bone formation by micro-CT analysis and osteoblastic markers (Runx2, OSX and OCN). Together, GTKO-pig cancellous bone showed better bone repair than WT-pig cancellous bone.
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Data source: Supplementary material, https://www.frontiersin.org/articles/10.3389/fbioe.2022.990769/full#supplementary-material
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Copyright 2022 The author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. (https://creativecommons.org/licenses/by/4.0/)