Long-term in vivo chimeric cells tracking in non-human primate

  • Junmo Wu 1,2 ,
  • Yu Kang 1,2 ,
  • Xiang Luo 1,2 ,
  • Shaoxing Dai 1,2 ,
  • Yuxi Shi 1,2 ,
  • Zhuoyao Li 1,2 ,
  • Zengli Tang 1,2 ,
  • Zhenzhen Chen 1,2 ,
  • Ran Zhu 1,2 ,
  • Pengpeng Yang 1,2 ,
  • Zifan Li 1,2 ,
  • Hong Wang 1,2 ,
  • Xinglong Chen 1,2 ,
  • Ziyi Zhao 1,2 ,
  • Weizhi Ji , 1,2 ,
  • Yuyu Niu , 1,2,3
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  • 1. State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming 650500, China
  • 2. Yunnan Key Laboratory of Primate Biomedical Research, Kunming 650500, China
  • 3. Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China
wji@lpbr.cn
niuyy@lpbr.cn

Received date: 27 Aug 2023

Accepted date: 31 Aug 2023

Published date: 15 Mar 2024

Copyright

2023 The Author(s) 2023. Published by Oxford University Press on behalf of Higher Education Press.

Abstract

Non-human primates (NHPs) are increasingly used in preclinical trials to test the safety and efficacy of biotechnology therapies. Nonetheless, given the ethical issues and costs associated with this model, it would be highly advantageous to use NHP cellular models in clinical studies. However, developing and maintaining the naïve state of primate pluripotent stem cells (PSCs) remains difficult as does in vivo detection of PSCs, thus limiting biotechnology application in the cynomolgus monkey. Here, we report a chemically defined, xeno-free culture system for culturing and deriving monkey PSCs in vitro. The cells display global gene expression and genome-wide hypomethylation patterns distinct from monkey-primed cells. We also found expression of signaling pathways components that may increase the potential for chimera formation. Crucially for biomedical applications, we were also able to integrate bioluminescent reporter genes into monkey PSCs and track them in chimeric embryos in vivo and in vitro. The engineered cells retained embryonic and extra-embryonic developmental potential. Meanwhile, we generated a chimeric monkey carrying bioluminescent cells, which were able to track chimeric cells for more than 2 years in living animals. Our study could have broad utility in primate stem cell engineering and in utilizing chimeric monkey models for clinical studies.

Cite this article

Junmo Wu , Yu Kang , Xiang Luo , Shaoxing Dai , Yuxi Shi , Zhuoyao Li , Zengli Tang , Zhenzhen Chen , Ran Zhu , Pengpeng Yang , Zifan Li , Hong Wang , Xinglong Chen , Ziyi Zhao , Weizhi Ji , Yuyu Niu . Long-term in vivo chimeric cells tracking in non-human primate[J]. Protein & Cell, 2024 , 15(3) : 207 -222 . DOI: 10.1093/procel/pwad049

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