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Cross-species blastocyst chimerism between nonhuman primates using iPSCs

Morteza Roodgar, Fabian P. Suchy, Vivek Bajpai, Jose G. Viches-Moure, Joydeep Bhadury, Angelos Oikonomopoulos, Joseph C. Wu, Joseph L. Mankowski, Kyle M. Loh, Hiromitsu Nakauchi, Catherine A. VandeVoort, Michael P. Snyder
doi: https://doi.org/10.1101/635250
Morteza Roodgar
1Department of Genetics, Stanford University, Stanford, California, 94305, USA
2Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California, 94305, USA
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Fabian P. Suchy
2Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California, 94305, USA
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Vivek Bajpai
2Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California, 94305, USA
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Jose G. Viches-Moure
3Department of Comparative Medicine, Stanford University, Stanford, California, 94305, USA
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Joydeep Bhadury
2Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California, 94305, USA
7Institute of Biomedicine, Sahlgrenska University Hospital, University of Gothenburg, SE 413 45, Gothenburg, Sweden
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Angelos Oikonomopoulos
5Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California, 94305, USA
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Joseph C. Wu
5Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California, 94305, USA
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Joseph L. Mankowski
6Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA
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Kyle M. Loh
2Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California, 94305, USA
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Hiromitsu Nakauchi
1Department of Genetics, Stanford University, Stanford, California, 94305, USA
2Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California, 94305, USA
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  • For correspondence: cavandevoort@ucdavis.edu nakauchi@stanford.edu mpsnyder@stanford.edu
Catherine A. VandeVoort
4California National Primate Research Center and Department of Obstetrics and Gynecology, University of California, Davis, CA, USA
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  • For correspondence: cavandevoort@ucdavis.edu nakauchi@stanford.edu mpsnyder@stanford.edu
Michael P. Snyder
1Department of Genetics, Stanford University, Stanford, California, 94305, USA
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  • For correspondence: cavandevoort@ucdavis.edu nakauchi@stanford.edu mpsnyder@stanford.edu
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Summary

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.

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Posted June 04, 2019.
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Cross-species blastocyst chimerism between nonhuman primates using iPSCs
Morteza Roodgar, Fabian P. Suchy, Vivek Bajpai, Jose G. Viches-Moure, Joydeep Bhadury, Angelos Oikonomopoulos, Joseph C. Wu, Joseph L. Mankowski, Kyle M. Loh, Hiromitsu Nakauchi, Catherine A. VandeVoort, Michael P. Snyder
bioRxiv 635250; doi: https://doi.org/10.1101/635250
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Cross-species blastocyst chimerism between nonhuman primates using iPSCs
Morteza Roodgar, Fabian P. Suchy, Vivek Bajpai, Jose G. Viches-Moure, Joydeep Bhadury, Angelos Oikonomopoulos, Joseph C. Wu, Joseph L. Mankowski, Kyle M. Loh, Hiromitsu Nakauchi, Catherine A. VandeVoort, Michael P. Snyder
bioRxiv 635250; doi: https://doi.org/10.1101/635250

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