RT Journal Article
SR Electronic
T1 Cross-species blastocyst chimerism between nonhuman primates using iPSCs
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 635250
DO 10.1101/635250
A1 Morteza Roodgar
A1 Fabian P. Suchy
A1 Vivek Bajpai
A1 Jose G. Viches-Moure
A1 Joydeep Bhadury
A1 Angelos Oikonomopoulos
A1 Joseph C. Wu
A1 Joseph L. Mankowski
A1 Kyle M. Loh
A1 Hiromitsu Nakauchi
A1 Catherine A. VandeVoort
A1 Michael P. Snyder
YR 2019
UL http://biorxiv.org/content/early/2019/06/04/635250.abstract
AB Through the production of chimeric animals, induced pluripotent stem cells (iPSCs) can generate personalized organs with diverse applications for both basic research and translational medicine. This concept was first validated in rodents by forming a rat pancreas in mice and vice versa. However, the potential use of human iPSCs to generate xenogenic organs in other species is technically and ethically difficult. Recognizing these concerns, we explored the generation of chimeric nonhuman primates (NHP) embryos, by injecting either chimpanzee or pig-tailed macaque iPSCs into rhesus macaque embryos. We first derived iPSCs from chimpanzees and pig-tailed macaques. We found that the chimpanzee iPSCs mixed well with human iPSCs during in vitro co-culture and differentiation. The differentiation of mixed human and chimpanzee iPSCs formed functioning cardiomyocyte layers in vitro, whereas human or chimpanzee iPSC mixed with pig-tailed macaque or mouse cells do not; these results indicate that chimpanzee and human cells are closely related in function. Considering the ethical aspects of injecting human iPSCs into nonhuman primate blastocysts, we tested whether chimpanzee iPSCs injected into 99 macaque 5-day-old embryos formed cross-species chimeras two days after injection. Strikingly, the chimpanzee iPSCs survived, proliferated and integrated near the inner cell mass (ICM) of rhesus macaque embryos. These findings highlight the broad potential of primate iPSCs in forming cross-species chimeras beyond rodents and provides a foundational basis for organ generation using human iPSCs.