Grape Exosome-like Nanoparticles Induce Intestinal Stem Cells and Protect Mice From DSS-Induced Colitis

作者：Songwen Ju, Jingyao Mu, Terje Dokland, Xiaoying Zhuang, Qilong Wang, Hong Jiang, Xiaoyu Xiang, Zhongbin Deng, Baomei Wang, Lifeng Zhang, Mary R. Roth, Ruth Welti, James A. Mobley, Yan Jun, Donald Ray Miller, Huang‐Ge Zhang · 发表于：Molecular Therapy · 年份：2013 · DOI：10.1038/mt.2013.64 · 被引用次数：872 · 研究领域：Extracellular vesicles in disease、Tissue Engineering and Regenerative Medicine

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.