期刊
JOURNAL OF CONTROLLED RELEASE
卷 347, 期 -, 页码 508-520出版社
ELSEVIER
DOI: 10.1016/j.jconrel.2022.05.028
关键词
Stem cell oral delivery; Hydrogel microcapsule with a thin oil layer; Colonic inflammation; Gut microbiota; Microfluidics
资金
- National Research Foundation of Korea (NRF) - Korea government (MSIT) [2019R1A2C1088927, 2018R1A5A2025272, 2021R1A4A1022206]
- National Research Foundation of Korea [2019R1A2C1088927] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
A strategy utilizing hydrogel microcapsules as an oral carrier enhances the survival and retention of mesenchymal stem cells in the gastrointestinal tract, effectively treating inflammatory bowel disease in a mouse model.
Mesenchymal stem cells (MSCs) are an attractive candidate for the treatment of inflammatory bowel disease (IBD), but their poor delivery rate to an inflamed colon is a major factor hampering the clinical potential of stem cell therapies. Moreover, there remains a formidable hurdle to overcome with regard to survival and homing in to injured sites. Here, we develop a strategy utilizing monodisperse hydrogel microcapsules with a thin intermediate oil layer prepared by a triple-emulsion drop-based microfluidic approach as an in-situ oral delivering carrier. The oral delivery of stem-cell-loaded hydrogel microcapsules (SC-HM) enhances MSC survival and retention in the hostile stomach environment due to the intermediate oil layer and low value of the overall stiffness, facilitating programmable cell release during gastrointestinal peristalsis. SC-HM is shown to induce tissue repair, reduce the colonic macrophage infiltration responsible for the secretion of the pro-inflammatory factors, and significantly mitigate the severity of IBD in a mouse model, where MSCs released by SC-HM successfully accumulate at the colonic crypt. Moreover, a metagenomics analysis reveals that SC-HM ameliorates the dysbiosis of specific bacterial genera, including Bacteroides acidifaciens, Lactobacillus (L.) gasseri, Lactobacillus reuteri, and L. intestinalis, implying optimization of the microorganism's composition and abundance. These findings demonstrate that SC-HM is a potential IBD treatment candidate.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据