Functional engraftment of colon epithelium expanded in vitro from a single adult Lgr5 + stem cell

Shiro Yui, Tetsuya Nakamura, Toshiro Sato, Yasuhiro Nemoto, Tomohiro Mizutani, Xiu Zheng, Shizuko Ichinose, Takashi Nagaishi, Ryuichi Okamoto, Kiichiro Tsuchiya, Hans Clevers, Mamoru Watanabe

Research output: Contribution to journalArticle

420 Citations (Scopus)

Abstract

Adult stem-cell therapy holds promise for the treatment of gastrointestinal diseases. Here we describe methods for long-term expansion of colonic stem cells positive for leucine-rich repeat containing G protein-coupled receptor 5 (Lgr5 + cells) in culture. To test the transplantability of these cells, we reintroduced cultured GFP + colon organoids into superficially damaged mouse colon. The transplanted donor cells readily integrated into the mouse colon, covering the area that lacked epithelium as a result of the introduced damage in recipient mice. At 4 weeks after transplantation, the donor-derived cells constituted a single-layered epithelium, which formed self-renewing crypts that were functionally and histologically normal. Moreover, we observed long-term (>6 months) engraftment with transplantation of organoids derived from a single Lgr5 + colon stem cell after extensive in vitro expansion. These data show the feasibility of colon stem-cell therapy based on the in vitro expansion of a single adult colonic stem cell.

Original languageEnglish
Pages (from-to)618-623
Number of pages6
JournalNature medicine
Volume18
Issue number4
DOIs
Publication statusPublished - 2012 Apr 1

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Dive into the research topics of 'Functional engraftment of colon epithelium expanded in vitro from a single adult Lgr5 <sup>+</sup> stem cell'. Together they form a unique fingerprint.

  • Cite this

    Yui, S., Nakamura, T., Sato, T., Nemoto, Y., Mizutani, T., Zheng, X., Ichinose, S., Nagaishi, T., Okamoto, R., Tsuchiya, K., Clevers, H., & Watanabe, M. (2012). Functional engraftment of colon epithelium expanded in vitro from a single adult Lgr5 + stem cell. Nature medicine, 18(4), 618-623. https://doi.org/10.1038/nm.2695