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

研究成果: Article査読

485 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)618-623
ページ数6
ジャーナルNature medicine
18
4
DOI
出版ステータスPublished - 2012 4

ASJC Scopus subject areas

  • 生化学、遺伝学、分子生物学(全般)

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