期刊
SCIENTIFIC REPORTS
卷 10, 期 1, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41598-020-60672-5
关键词
-
资金
- Children's Discovery Institute of Washington University in St. Louis
- St. Louis Children's Hospital [CDI-CORE-2015-505, MI-FR2017-596, MI-F-2017-629]
- National Institutes of Health [R01 DK-104698, R03DK111473, R01DK118568, R01 DK-106382, R01DK-112378, R01DK109384, K01DK109081, K08DK101608, 4T32HD043010-14, 3T32DK007130-45S1]
- Digestive Diseases Research Core Center Grant NIDDK [P30 DK052574]
- Children's Surgical Sciences Research Institute of the St. Louis Children's Hospital
- Association for Academic Surgery Foundation
- March of Dimes Foundation [5-FY17-79]
- Department of Pediatrics at Washington University School of Medicine, St. Louis
- Lawrence C. Pakula MD IBD Research, Innovation, and Education Fund
- Washington University School of Medicine
- Children's Discovery Institute of Washington University
- Foundation for Barnes-Jewish Hospital [3770]
The development and physiologic role of small intestine (SI) vasculature is poorly studied. This is partly due to a lack of targetable, organ-specific markers for in vivo studies of two critical tissue components: endothelium and stroma. This challenge is exacerbated by limitations of traditional cell culture techniques, which fail to recapitulate mechanobiologic stimuli known to affect vessel development. Here, we construct and characterize a 3D in vitro microfluidic model that supports the growth of patient-derived intestinal subepithelial myofibroblasts (ISEMFs) and endothelial cells (ECs) into perfused capillary networks. We report how ISEMF and EC-derived vasculature responds to physiologic parameters such as oxygen tension, cell density, growth factors, and pharmacotherapy with an antineoplastic agent (Erlotinib). Finally, we demonstrate effects of ISEMF and EC co-culture on patient-derived human intestinal epithelial cells (HIECs), and incorporate perfused vasculature into a gut-on-a-chip (GOC) model that includes HIECs. Overall, we demonstrate that ISEMFs possess angiogenic properties as evidenced by their ability to reliably, reproducibly, and quantifiably facilitate development of perfused vasculature in a microfluidic system. We furthermore demonstrate the feasibility of including perfused vasculature, including ISEMFs, as critical components of a novel, patient-derived, GOC system with translational relevance as a platform for precision and personalized medicine research.
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