Compensation of Disabled Organogeneses in Genetically Modified Pig Fetuses by Blastocyst Complementation

Hitomi Matsunari, Masahito Watanabe, Koki Hasegawa, Ayuko Uchikura, Kazuaki Nakano, Kazuhiro Umeyama, Hideki Masaki, Sanae Hamanaka, Tomoyuki Yamaguchi, Masaki Nagaya, Ryuichi Nishinakamura, Hiromitsu Nakauchi, Hiroshi Nagashima

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

We have previously established a concept of developing exogenic pancreas in a genetically modified pig fetus with an apancreatic trait, thereby proposing the possibility of in vivo generation of functional human organs in xenogenic large animals. In this study, we aimed to demonstrate a further proof-of-concept of the compensation for disabled organogeneses in pig, including pancreatogenesis, nephrogenesis, hepatogenesis, and vasculogenesis. These dysorganogenetic phenotypes could be efficiently induced via genome editing of the cloned pigs. Induced dysorganogenetic traits could also be compensated by allogenic blastocyst complementation, thereby proving the extended concept of organ regeneration from exogenous pluripotent cells in empty niches during various organogeneses. These results suggest that the feasibility of blastocyst complementation using genome-edited cloned embryos permits experimentation toward the in vivo organ generation in pigs from xenogenic pluripotent cells. In this article, Nagashima and colleagues generated various cloned pig fetuses with dysorganogenetic phenotypes by editing master regulatory genes for pancreatogenesis, nephrogenesis, hepatogenesis, and vasculogenesis. They also demonstrate that these disabled organogeneses can be compensated by allogenic blastocyst complementation, thereby enabling use of the genetically modified pig fetuses for in vivo organ generation studies.

Original languageEnglish
Pages (from-to)21-33
Number of pages13
JournalStem Cell Reports
Volume14
Issue number1
DOIs
Publication statusPublished - 14 Jan 2020

Keywords

  • blastocyst complementation
  • cloned pig
  • organ regeneration
  • organogenesis
  • pluripotent stem cells

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    Matsunari, H., Watanabe, M., Hasegawa, K., Uchikura, A., Nakano, K., Umeyama, K., Masaki, H., Hamanaka, S., Yamaguchi, T., Nagaya, M., Nishinakamura, R., Nakauchi, H., & Nagashima, H. (2020). Compensation of Disabled Organogeneses in Genetically Modified Pig Fetuses by Blastocyst Complementation. Stem Cell Reports, 14(1), 21-33. https://doi.org/10.1016/j.stemcr.2019.11.008