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

402 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

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Adult Stem Cells
Stem cells
Colon
Epithelium
Organoids
Stem Cells
Cell- and Tissue-Based Therapy
Transplantation
Gastrointestinal Diseases
G-Protein-Coupled Receptors
Leucine
Cultured Cells
Cell Culture Techniques
In Vitro Techniques

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Yui, S., Nakamura, T., Sato, T., Nemoto, Y., Mizutani, T., Zheng, X., ... 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

Functional engraftment of colon epithelium expanded in vitro from a single adult Lgr5 + stem cell. / Yui, Shiro; Nakamura, Tetsuya; Sato, Toshiro; Nemoto, Yasuhiro; Mizutani, Tomohiro; Zheng, Xiu; Ichinose, Shizuko; Nagaishi, Takashi; Okamoto, Ryuichi; Tsuchiya, Kiichiro; Clevers, Hans; Watanabe, Mamoru.

In: Nature Medicine, Vol. 18, No. 4, 04.2012, p. 618-623.

Research output: Contribution to journalArticle

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, vol. 18, no. 4, pp. 618-623. https://doi.org/10.1038/nm.2695
Yui, Shiro ; Nakamura, Tetsuya ; Sato, Toshiro ; Nemoto, Yasuhiro ; Mizutani, Tomohiro ; Zheng, Xiu ; Ichinose, Shizuko ; Nagaishi, Takashi ; Okamoto, Ryuichi ; Tsuchiya, Kiichiro ; Clevers, Hans ; Watanabe, Mamoru. / Functional engraftment of colon epithelium expanded in vitro from a single adult Lgr5 + stem cell. In: Nature Medicine. 2012 ; Vol. 18, No. 4. pp. 618-623.
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