De Novo Mutations in Mitochondrial DNA of iPSCs Produce Immunogenic Neoepitopes in Humans

Long-term culture and differentiation of iPSC lead to mtDNA mutations that are not naturally selected against by the immune system. A single nucleotide mutation in the mtDNA giving rise to neoantigens triggers a strong immune response and may contribute to the rejection of grafted cells and thus could be of significant relevance to transplantation approaches in regenerative medicine.