期刊
NATURE MEDICINE
卷 18, 期 4, 页码 618-623出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nm.2695
关键词
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资金
- Japanese Ministry of Education, Culture, Sports, Science and Technology
- Ministry of Health, Labour and Welfare of Japan
- European Research Council
- Dutch Cancer Foundation
- Grants-in-Aid for Scientific Research [23890204, 24790684, 23130506, 22590694, 24590936, 23790777, 21590806, 22590695, 23590934, 21590805, 22117508, 24590937, 22229005, 23659394, 24112508, 21590803, 22590696, 24390186] Funding Source: KAKEN
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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