期刊
MOLECULAR THERAPY
卷 21, 期 7, 页码 1345-1357出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/mt.2013.64
关键词
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资金
- National Institutes of Health [RO1CA137037, R01CA107181, RO1AT004294, RO1CA116092]
- Louisville Veterans Administration Medical Center (VAMC) Merit Review Grants
- Susan G Komen Breast Cancer Foundation
- National Science Foundation [EPS 0236913, DBI 0521587, DBI 1228622, MCB 0920663]
- Kansas Technology Enterprise Corporation
- K-IDeA Networks of Biomedical Research Excellence (INBRE) of National Institute of Health [P20RR16475]
- Kansas State University
- Direct For Biological Sciences
- Div Of Biological Infrastructure [1228622] Funding Source: National Science Foundation
- Div Of Molecular and Cellular Bioscience
- Direct For Biological Sciences [0920663] Funding Source: National Science Foundation
Food-derived exosome-like nanoparticles pass through the intestinal tract throughout our lives, but little is known about their impact or function. Here, as a proof of concept, we show that the cells targeted by grape exosome-like nanoparticles (GELNs) are intestinal stem cells whose responses underlie the GELN-mediated intestinal tissue remodeling and protection against dextran sulfate sodium (DSS)-induced colitis. This finding is further supported by the fact that coculturing of crypt or sorted Lgr5(+) stem cells with GELNs markedly improved organoid formation. GELN lipids play a role in induction of Lgr5(+) stem cells, and the liposome-like nanoparticles (LLNs) assembled with lipids from GELNs are required for in vivo targeting of intestinal stem cells. Blocking beta-catenin-mediated signaling pathways of GELN recipient cells attenuates the production of Lgr5(+) stem cells. Thus, GELNs not only modulate intestinal tissue renewal processes, but can participate in the remodeling of it in response to pathological triggers.
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