Reduction in Xenogeneic Epitopes on Porcine Endothelial Cells by Periodate Oxidation
Jonas Thom1, Nathalie Roters2, Slavica Schuemann2,3
1Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Hannover Medical School, 30625 Hannover, Germany.
Biomedicines
|July 27, 2024
Summary
Chemical modification of porcine cells using sodium periodate (NaIO4) oxidation effectively reduces immune-triggering glycan antigens like alpha-Gal (Galili antigen). This approach maintains cell viability, offering a promising strategy for pig-to-human xenotransplantation by preventing antibody-mediated rejection.
Area of Science:
- Biochemistry
- Immunology
- Transplantation Science
Background:
- Humoral immune responses against porcine cells are a major barrier to pig-to-human xenotransplantation.
- Key xenoantigens include alpha-Gal (Galili antigen) and Neu5Gc, with other differences in glycosylation also contributing to immune recognition.
- A broad range of glycan epitopes on porcine cells may elicit xeno-reactive immune responses.
Purpose of the Study:
- To chemically modify porcine cellular surface glycans using sodium periodate (NaIO4) oxidation.
- To assess the impact of NaIO4 oxidation on cell viability and immunogenicity.
- To determine the effectiveness of NaIO4 oxidation in reducing specific xenoantigens.
Main Methods:
- Porcine endothelial cells were oxidized with varying concentrations of NaIO4 at different temperatures and conditions.
- Cell viability was assessed using live/dead assays.
- Oxidation of alpha-Gal epitopes was quantified using isolectin-B4 (IL-B4) staining, and overall immunogenicity was measured by human serum antibody binding.
Main Results:
- NaIO4 treatment reduced the binding of alpha-Gal-specific IL-B4 and human serum antibodies.
- Cytotoxicity was observed at higher temperatures and longer treatment durations.
- Optimal conditions (2 mM NaIO4, 60 min, 4 °C) preserved cell viability while significantly reducing alpha-Gal epitopes, irrespective of static or flow conditions.
Conclusions:
- Sodium periodate (NaIO4) can effectively oxidize glycan epitopes on living cells while maintaining viability.
- This glycan modification strategy shows promise for preventing immune reactions caused by preformed anti-glycan antibodies in xenotransplantation.
- The method offers a potential solution to overcome humoral immune barriers in xenotransplantation.
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