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

TY - JOUR

T1 - Functional engraftment of colon epithelium expanded in vitro from a single adult Lgr5(+) stem cell

AU - Yui, S.

AU - Nakamura, T.

AU - Sato, T.

AU - Nemoto, Y.

AU - Mizutani, T.

AU - Zheng, X.

AU - Ichinose, S.

AU - Nagaishi, T.

AU - Okamoto, R.

AU - Tsuchiya, K.

AU - Clevers, H.

AU - Watanabe, M.

N1 - Reporting year: 2012

PY - 2012

Y1 - 2012

N2 - 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.

AB - 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.

U2 - 10.1038/nm.2695

DO - 10.1038/nm.2695

M3 - Article

SN - 1078-8956

VL - 18

SP - 618

EP - 623

JO - Nature Medicine

JF - Nature Medicine

IS - 4

ER -