AUTHOR=Wang Wenhao , Lu Jiansen , Song Ying , Zeng Chun , Wang Yongkui , Yang Cheng , Huang Bin , Dai Yifan , Yang Jian , Lai Liangxue , Wang Liping , Cai Daozhang , Bai Xiaochun
TITLE=Repair of bone defects in rhesus monkeys with α1,3-galactosyltransferase-knockout pig cancellous bone
JOURNAL=Frontiers in Bioengineering and Biotechnology
VOLUME=10
YEAR=2022
URL=https://www.frontiersin.org/journals/bioengineering-and-biotechnology/articles/10.3389/fbioe.2022.990769
DOI=10.3389/fbioe.2022.990769
ISSN=2296-4185
ABSTRACT=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 α1,3-galactosyltransferase (α1,3-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-γ 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-γ 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.