title: Grape exosome-like nanoparticles induce intestinal stem cells and protect mice from DSS-induced colitis.
abstract: 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 β-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.
authors.affiliation: Department of Microbiology & Immunology, Brown Cancer Center, University of Louisville, Louisville, Kentucky, USA.
authors.forename: Songwen
authors.initials: S
authors.lastname: Ju
authors.forename: Jingyao
authors.initials: J
authors.lastname: Mu
authors.forename: Terje
authors.initials: T
authors.lastname: Dokland
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Zhuang
authors.forename: Qilong
authors.initials: Q
authors.lastname: Wang
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Xiang
authors.forename: Zhong-Bin
authors.initials: ZB
authors.lastname: Deng
authors.forename: Baomei
authors.initials: B
authors.lastname: Wang
authors.forename: Lifeng
authors.initials: L
authors.lastname: Zhang
authors.forename: Mary
authors.initials: M
authors.lastname: Roth
authors.forename: Ruth
authors.initials: R
authors.lastname: Welti
authors.forename: James
authors.initials: J
authors.lastname: Mobley
authors.forename: Yan
authors.initials: Y
authors.lastname: Jun
authors.forename: Donald
authors.initials: D
authors.lastname: Miller
authors.forename: Huang-Ge
authors.initials: HG
authors.lastname: Zhang
mesh_terms: D000818:Animals; D003092:Colitis / Q000139:chemically induced* / Q000517:prevention & control*; D016264:Dextran Sulfate / Q000633:toxicity*; D007422:Intestines / Q000166:cytology*; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000627:therapeutic use*; D013234:Stem Cells / Q000166:cytology*; D027843:Vitis / Q000737:chemistry*
chemical_list: D016264:Dextran Sulfate