@article{8d9d0eb754ee4f08918ca1d182a532b0,
title = "Patient-derived small intestinal myofibroblasts direct perfused, physiologically responsive capillary development in a microfluidic Gut-on-a-Chip Model",
abstract = "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.",
author = "Seiler, {Kristen M.} and Adam Bajinting and Alvarado, {David M.} and Traore, {Mahama A.} and Binkley, {Michael M.} and Goo, {William H.} and Lanik, {Wyatt E.} and Jocelyn Ou and Usama Ismail and Micah Iticovici and King, {Cristi R.} and VanDussen, {Kelli L.} and Swietlicki, {Elzbieta A.} and Vered Gazit and Jun Guo and Luke, {Cliff J.} and Thaddeus Stappenbeck and Ciorba, {Matthew A.} and George, {Steven C.} and Meacham, {J. Mark} and Rubin, {Deborah C.} and Misty Good and Warner, {Brad W.}",
note = "Funding Information: Portions of this study were presented at the American Academy of Pediatrics National Conference on September 17th, 2017 in Chicago, IL and Digestive Diseases Week, 2018 in Washington, D.C. This work was supported by the Children{\textquoteright}s Discovery Institute of Washington University in St. Louis and St. Louis Children{\textquoteright}s Hospital MI-FR-2017-596 (M.G.) and MI-F-2017-629 (K.M.S.); National Institutes of Health grants R01 DK-104698 (B.W.W.), R03DK111473 (M.G), R01DK118568 (M.G.), R01 DK-106382 (D.C.R.), R01DK-112378 (D.C.R.), R01DK109384 (M.A.C.); K01DK109081 (K.L.V.), K08DK101608 (M.G.), 4T32HD043010-14 (K.M.S.), 3T32DK007130-45S1 (A.B.), and Digestive Diseases Research Core Center Grant NIDDK P30 DK052574; the Children{\textquoteright}s Surgical Sciences Research Institute of the St. Louis Children{\textquoteright}s Hospital (B.W.W.); the Association for Academic Surgery Foundation (K.M.S.); March of Dimes Foundation Grant No. 5-FY17-79 (M.G.), and the Department of Pediatrics at Washington University School of Medicine, St. Louis (M.G.). Philanthropic support was provided by the Givin{\textquoteright} it all for Guts Foundation (https://givinitallforguts.org/, M.A.C.) and the Lawrence C. Pakula MD IBD Research, Innovation, and Education Fund (M.A.C. and D.M.A.); Imaging using the Zeiss LSM 880 II Airyscan FAST Confocal Microscope was performed using Washington University Center for Cellular Imaging (WUCCI), supported by Washington University School of Medicine, The Children{\textquoteright}s Discovery Institute of Washington University and St. Louis Children{\textquoteright}s Hospital (CDI-CORE-2015-505), and the Foundation for Barnes-Jewish Hospital (3770). Mold fabrication was performed in the Institute of Materials Science & Engineering (IMSE) microfabrication facility at Washington University. Publisher Copyright: {\textcopyright} 2020, The Author(s).",
year = "2020",
month = dec,
day = "1",
doi = "10.1038/s41598-020-60672-5",
language = "English",
volume = "10",
journal = "Scientific reports",
issn = "2045-2322",
number = "1",
}