Vascularized Liver Organoids Generated Using Induced Hepatic Tissue and Dynamic Liver-Specific Microenvironment as a Drug Testing Platform

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Title
Vascularized Liver Organoids Generated Using Induced Hepatic Tissue and Dynamic Liver-Specific Microenvironment as a Drug Testing Platform
Author(s)
Yoonhee Jin; Jin Kim; Jung Seung Lee; Sungjin Min; Suran Kim; Da-Hee Ahn; Yun-Gon Kim; Seung-Woo Cho
Publication Date
2018-09
Journal
ADVANCED FUNCTIONAL MATERIALS, v.28, no.37, pp.1801954 -
Publisher
WILEY-V C H VERLAG GMBH
Abstract
Induced hepatic (iHep) cells generated by direct reprogramming have been proposed as cell sources for drug screening and regenerative medicine. However, the practical use of a 3D hepatic tissue culture comprised of iHep cells for drug screening and toxicology testing has not been demonstrated. In this study, a 3D vascularized liver organoid composed of iHep cells and a decellularized liver extracellular matrix (LEM) cultured in a microfluidic system is demonstrated. iHep cells are generated by transfection with polymer nanoparticles and plasmids expressing hepatic transcription factors. The iHep cells are cocultured with endothelial cells in the 3D LEM hydrogel in a microfluidic-based cell culture device with a continuous dynamic flow of media. The resultant 3D vascularized liver organoids maintained under this physiologically relevant culture microenvironment exhibit improved hepatic functionalities, metabolic activity, biosynthetic activity, and drug responses. Finally, the feasibility of using the iHep-based 3D liver organoid as a high-throughput drug screening platform, as well as its use in a multiorgan model comprised of multiple internal organoids is confirmed. The study suggests that a combined strategy of direct reprogramming, matrix engineering, and microfluidics can be used to develop a highly functional, standardized, drug screening, and toxicological analysis platform. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinhei
URI
https://pr.ibs.re.kr/handle/8788114/5186
ISSN
1616-301X
Appears in Collections:
Center for Nanomedicine (나노의학 연구단) > Journal Papers
Files in This Item:
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