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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 | Mi-Young Son
Nature communications | 2018

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.

Pubmed ID: 30072687

Associated grants

  • Agency: National Research Foundation of Korea (NRF), International
    Id: 2016R1A2B4013501
  • Agency: Korea Research Institute of Bioscience and Biotechnology (KRIBB), International
    Id: KRIBB Research Initiative Program

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