西亚试剂：Functional engraftment of colon epithelium expanded in vitr

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

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.

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