Functional engraftment of colon epithelium expanded in vitro from a single adult Lgr5+ stem cell
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- 11 March 2012
- journal article
- Published by Springer Science and Business Media LLC in Nature Medicine
- Vol. 18 (4), 618-623
- https://doi.org/10.1038/nm.2695
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.Keywords
This publication has 34 references indexed in Scilit:
- The intestinal stem cellGenes & Development, 2008
- Bmi1 is expressed in vivo in intestinal stem cellsNature Genetics, 2008
- Identification of stem cells in small intestine and colon by marker gene Lgr5Nature, 2007
- Hepatocyte growth factor promotes colonic epithelial regeneration via Akt signalingAmerican Journal of Physiology-Gastrointestinal and Liver Physiology, 2007
- R-spondin1 Is a High Affinity Ligand for LRP6 and Induces LRP6 Phosphorylation and β-Catenin SignalingOnline Journal of Public Health Informatics, 2007
- Engraftment of Mucosal Stem Cells into Murine Jejunum is Dependent on Optimal Dose of CellsJournal of Surgical Research, 2006
- Intestinal Epithelial Stem Cells and ProgenitorsMethods in Enzymology, 2006
- Chronic Treatment with the γ-Secretase Inhibitor LY-411,575 Inhibits β-Amyloid Peptide Production and Alters Lymphopoiesis and Intestinal Cell DifferentiationOnline Journal of Public Health Informatics, 2004
- Hepatocyte Growth Factor Facilitates Colonic Mucosal Repair in Experimental Ulcerative Colitis in RatsThe Journal of pharmacology and experimental therapeutics, 2003
- Clonogenic growth of epithelial cells from normal colonic mucosa from both mice and humansGastroenterology, 1999