Interleukin-2 induces the in vitro maturation of human pluripotent stem cell-derived intestinal organoids

Kwang Bo Jung, Hana Lee, Ye Seul Son, Mi-Ok Lee, Young-Dae Kim, Soo Jin Oh, Ohman Kwon, Sunwha Cho, Hyun-Soo Cho, Dae-Soo Kim, Jung-Hwa Oh, Matthias Zilbauer, Jeong-Ki Min, Cho-Rok Jung (), Janghwan Kim () and Mi-Young Son ()
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Kwang Bo Jung: Korea Research Institute of Bioscience and Biotechnology (KRIBB)
Hana Lee: Korea Research Institute of Bioscience and Biotechnology (KRIBB)
Ye Seul Son: Korea Research Institute of Bioscience and Biotechnology (KRIBB)
Mi-Ok Lee: Korea Research Institute of Bioscience and Biotechnology (KRIBB)
Young-Dae Kim: Korea Research Institute of Bioscience and Biotechnology (KRIBB)
Soo Jin Oh: University of Ulsan
Ohman Kwon: Korea Research Institute of Bioscience and Biotechnology (KRIBB)
Sunwha Cho: Korea Research Institute of Bioscience and Biotechnology (KRIBB)
Hyun-Soo Cho: Korea Research Institute of Bioscience and Biotechnology (KRIBB)
Dae-Soo Kim: Korea Research Institute of Bioscience and Biotechnology (KRIBB)
Jung-Hwa Oh: Korea Institute of Toxicology
Matthias Zilbauer: Cambridge Biomedical Campus
Jeong-Ki Min: Korea Research Institute of Bioscience and Biotechnology (KRIBB)
Cho-Rok Jung: Korea Research Institute of Bioscience and Biotechnology (KRIBB)
Janghwan Kim: Korea Research Institute of Bioscience and Biotechnology (KRIBB)
Mi-Young Son: Korea Research Institute of Bioscience and Biotechnology (KRIBB)

Nature Communications, 2018, vol. 9, issue 1, 1-13

Abstract: Abstract Human pluripotent stem cell (hPSC)-derived intestinal organoids (hIOs) form 3D structures organized into crypt and villus domains, making them an excellent in vitro model system for studying human intestinal development and disease. However, hPSC-derived hIOs still require in vivo maturation to fully recapitulate adult intestine, with the mechanism of maturation remaining elusive. Here, we show that the co-culture with human T lymphocytes induce the in vitro maturation of hIOs, and identify STAT3-activating interleukin-2 (IL-2) as the major factor inducing maturation. hIOs exposed to IL-2 closely mimic the adult intestinal epithelium and have comparable expression levels of mature intestinal markers, as well as increased intestine-specific functional activities. Even after in vivo engraftment, in vitro-matured hIOs retain their maturation status. The results of our study demonstrate that STAT3 signaling can induce the maturation of hIOs in vitro, thereby circumventing the need for animal models and in vivo maturation.

Date: 2018
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DOI: 10.1038/s41467-018-05450-8

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