Thom, J.; Roters, N.; Schuemann, S.; Andrée, B.; Buettner, F.F.R.; Hilfiker, A.; Goecke, T.; Ramm, R. Reduction in Xenogeneic Epitopes on Porcine Endothelial Cells by Periodate Oxidation. Biomedicines2024, 12, 1470.
Thom, J.; Roters, N.; Schuemann, S.; Andrée, B.; Buettner, F.F.R.; Hilfiker, A.; Goecke, T.; Ramm, R. Reduction in Xenogeneic Epitopes on Porcine Endothelial Cells by Periodate Oxidation. Biomedicines 2024, 12, 1470.
Thom, J.; Roters, N.; Schuemann, S.; Andrée, B.; Buettner, F.F.R.; Hilfiker, A.; Goecke, T.; Ramm, R. Reduction in Xenogeneic Epitopes on Porcine Endothelial Cells by Periodate Oxidation. Biomedicines2024, 12, 1470.
Thom, J.; Roters, N.; Schuemann, S.; Andrée, B.; Buettner, F.F.R.; Hilfiker, A.; Goecke, T.; Ramm, R. Reduction in Xenogeneic Epitopes on Porcine Endothelial Cells by Periodate Oxidation. Biomedicines 2024, 12, 1470.
Abstract
Background: Patterns of humoral immune responses represent a major hurdle in terms of pig-to-human xenotransplantation approaches. The best-known xenogeneic glycan antigens pre-sent in pigs are the αGal (Galili-antigen) and the non-human sialic acid Neu5Gc. As there are further differences between porcine and human cellular surface glycosylation, a much broader range of glycan epitopes with xeno-reactive relevance can be anticipated. Therefore, we set-out to chemically modify porcine cellular surface glycans in a global approach by applying sodium peri-odate (NaIO4) oxidation. Methods: Porcine endothelial cells were exposed to oxidation with 1 to 5 mM NaIO4 for different time periods at 37°C or 4°C and under static or dynamic conditions. The impact on cellular sur-vival was determined applying live/dead-assays. Oxidation of αGal-epitopes was assessed by flu-orescence microscopy-based quantification of isolectin-B4 (IL-B4) staining. Overall immunogenic-ity of porcine cells was determined by human serum antibody binding. Results: Treatment of porcine endothelial cells and tissues with NaIO4 led to a reduced binding of the αGal-specific IL-B4 and/or human serum antibodies. NaIO4 revealed to be cytotoxic when performed at elevated temperature and for prolonged time. However, by applying 2 mM NaIO4 for 60 min at 4°C a high extent of cellular viability and a relevant reduction of detectable αGal epitope were observed. No differences were detected irrespectively on whether the cells were oxi-dized under static or flow conditions. Conclusion: Glycan epitopes on living cells can be oxidized with NaIO4 while maintaining their viability. Accordingly, this strategy holds promise to prevent immune reactions mediated by pre-formed anti-glycan antibodies.
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
,
,
,
,
*
