International Journal of Stem Cells

  • 제15권1호
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  • Pages.104-111
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  • 2022
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  • 2005-3606(pISSN)
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  • 2005-5447(eISSN)
한국줄기세포학회 (Korean Society for Stem Cell Research)
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Generation of Highly Expandable Intestinal Spheroids Composed of Stem Cells

  • Ohman Kwon (Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Won Dong Yu (Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Ye Seul Son (Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Kwang Bo Jung (Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Hana Lee (Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Mi-Young Son (Korea Research Institute of Bioscience and Biotechnology (KRIBB))
  • 투고 : 2021.10.29
  • 심사 : 2022.01.25
  • 발행 : 2022.02.28
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초록

Many of early findings regarding intestinal stem cells (ISCs) and their niche in the human intestine have relied on colorectal cancer cell lines and labor-intensive and time-consuming mouse models. However, these models cannot accurately recapitulate the physiologically relevant aspects of human ISCs. In this study, we demonstrate a reliable and robust culture method for 3D expanding intestinal spheroids (InSexp) mainly comprising ISCs and progenitors, which can be derived from 3D human intestinal organoids (HIOs). We did functional chararcterization of InSexp derived from 3D HIOs, differentiated from human pluripotent stem cells, and optimization culture methods. Our results indicate that InSexp can be rapidly expanded and easily passaged, and show enhanced growth rates via WNT pathway activation. InSexp are capable of exponential cell expansion and cryopreservation. Furthermore, in vitro-matured HIO-derived InSexp proliferate faster than immature HIO-derived InSexp with preservation of the parental HIO characteristics. These findings may facilitate the development of scalable culture systems for the long-term maintenance of human ISCs and provide an alternative platform for studying ISC biology.

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과제정보

This work was supported by the Korean Fund for Regenerative Medicine (KFRM) grant funded by the Korea government(the Ministry of Science and ICT, the Ministry of Health & Welfare, 21A0404L1), a grant from the Technology Innovation Program (No. 20008777) funded by the Ministry of Trade, Industry & Energy (MOTIE, Korea), a grant from the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (NRF-2018M3A9H3023077/2021M3A9H3016046), the Center for Agricultural Microorganism and Enzyme (Project No. PJ015049) of Rural Development Administration, the KIST Institutional Program (Atmospheric Environment Research Program, 2E1390-21-P017), and the KRIBB Research Initiative Program (KGM4722223, KGS1102113). The funders had no role in the study design, data collection and analysis, decision to publish, and preparation of the manuscript.

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