MHC-identical and transgenic cynomolgus macaques for preclinical studies.

Cynomolgus macaques are useful experimental animals that are physiologically and genetically close to humans. We have developed two kinds of experimental usage of cynomolgus macaque: transplantation and disease models. First, we identified certain major histocompatibility complex (MHC) haplotypes including homozygotes and heterozygotes in cynomolgus macaques native to the Philippines, because they have less polymorphism in the MHC than that in other origins such as Vietnam and Indonesia. As a preclinical model of the induced pluripotent stem cell (iPSC) stock project, we established iPSCs from various types of MHC homozygous macaques, which were transplanted into compatible MHC heterozygous macaques, the iPSC stock project was experimentally shown to be effective. Second, to obtain disease models of cynomolgus macaques for studies on regenerative medicine including cell therapies, we established two kinds of genetic technology to modify cynomolgus macaques: transgenic technology and gene editing technology using CRISPR-Cas9. We will establish disease models, such as Alzheimer's disease and progeria (Werner syndrome). In future, we will distribute the MHC-identical cynomolgus monkeys and genetically modified macaques to researchers, especially those engaging in regenerative medicine.