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

Yoonhee Jin, Jin Kim, Jung Seung Lee, Sungjin Min, Suran Kim, Da Hee Ahn, Yun Gon Kim, Seung-Woo Cho

Research output: Contribution to journalArticle

9 Citations (Scopus)

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.

Original languageEnglish
Article number1801954
JournalAdvanced Functional Materials
Volume28
Issue number37
DOIs
Publication statusPublished - 2018 Sep 12

Fingerprint

liver
Liver
drugs
platforms
Tissue
Screening
screening
Microfluidics
Testing
cells
Pharmaceutical Preparations
matrices
toxicology
Tissue culture
plasmids
Transcription factors
Hydrogel
Endothelial cells
medicine
Cell culture

All Science Journal Classification (ASJC) codes

  • Electronic, Optical and Magnetic Materials
  • Biomaterials
  • Chemistry(all)
  • Materials Science(all)
  • Condensed Matter Physics
  • Electrochemistry

Cite this

Jin, Yoonhee ; Kim, Jin ; Lee, Jung Seung ; Min, Sungjin ; Kim, Suran ; Ahn, Da Hee ; Kim, Yun Gon ; Cho, Seung-Woo. / Vascularized Liver Organoids Generated Using Induced Hepatic Tissue and Dynamic Liver-Specific Microenvironment as a Drug Testing Platform. In: Advanced Functional Materials. 2018 ; Vol. 28, No. 37.
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Vascularized Liver Organoids Generated Using Induced Hepatic Tissue and Dynamic Liver-Specific Microenvironment as a Drug Testing Platform. / Jin, Yoonhee; Kim, Jin; Lee, Jung Seung; Min, Sungjin; Kim, Suran; Ahn, Da Hee; Kim, Yun Gon; Cho, Seung-Woo.

In: Advanced Functional Materials, Vol. 28, No. 37, 1801954, 12.09.2018.

Research output: Contribution to journalArticle

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