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

Nature medicine, 2012-04, Vol.18 (4), p.618-623 [Peer Reviewed Journal]

Copyright Nature Publishing Group Apr 2012 ;Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. 2012. ;ISSN: 1078-8956 ;EISSN: 1546-170X ;DOI: 10.1038/nm.2695 ;PMID: 22406745

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Title:
Functional engraftment of colon epithelium expanded in vitro from a single adult Lgr5⁺ stem cell
Author: Yui, Shiro ; Nakamura, Tetsuya ; Sato, Toshiro ; Nemoto, Yasuhiro ; Mizutani, Tomohiro ; Zheng, Xiu ; Ichinose, Shizuko ; Nagaishi, Takashi ; Okamoto, Ryuichi ; Tsuchiya, Kiichiro ; Clevers, Hans ; Watanabe, Mamoru
Subjects: Adult Stem Cells - metabolism ; Allografts ; Animals ; Body Weight - physiology ; Cell culture ; Cell therapy ; Cells, Cultured ; Cellular biology ; Chromogranin A - metabolism ; Colitis ; Colon ; Colon - cytology ; Colon - transplantation ; Crypts ; Cyclooxygenase 1 - metabolism ; Damage ; Dextran ; Dextran sulfate ; Dextrans ; DNA-Binding Proteins - deficiency ; Epithelium ; Epithelium - physiology ; Expansion ; Gastrointestinal diseases ; Gastrointestinal tract diseases ; Green Fluorescent Proteins - genetics ; In Vitro Techniques ; Intestine ; Ki-67 Antigen - metabolism ; Leucine ; Membrane Proteins - metabolism ; Mice ; Mice, Transgenic ; Organoids ; Organoids - cytology ; Organoids - physiology ; Proteins ; Receptors, G-Protein-Coupled - genetics ; Receptors, G-Protein-Coupled - metabolism ; Rhodamines - metabolism ; Small intestine ; Stem cell transplantation ; Stem cells ; Therapy ; Time Factors ; Transplantation ; Transplants
Is Part Of: Nature medicine, 2012-04, Vol.18 (4), p.618-623
Description: 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.
Publisher: United States: Nature Publishing Group
Language: English
Identifier: ISSN: 1078-8956
EISSN: 1546-170X
DOI: 10.1038/nm.2695
PMID: 22406745
Source: MEDLINE
ProQuest Central

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

Copyright Nature Publishing Group Apr 2012 ;Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. 2012. ;ISSN: 1078-8956 ;EISSN: 1546-170X ;DOI: 10.1038/nm.2695 ;PMID: 22406745

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