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Main Title: Generation of a 3D Liver Model Comprising Human Extracellular Matrix in an Alginate/Gelatin-Based Bioink by Extrusion Bioprinting for Infection and Transduction Studies
Author(s): Hiller, Thomas
Berg, Johanna
Elomaa, Laura
Röhrs, Viola
Ullah, Imran
Schaar, Katrin
Dietrich, Ann-Christin
Al-Zeer, Munir A.
Kurtz, Andreas
Hocke, Andreas C.
Hippenstiel, Stefan
Fechner, Henry
Weinhart, Marie
Kurreck, Jens
Type: Article
Language Code: en
Abstract: Bioprinting is a novel technology that may help to overcome limitations associated with two-dimensional (2D) cell cultures and animal experiments, as it allows the production of three-dimensional (3D) tissue models composed of human cells. The present study describes the optimization of a bioink composed of alginate, gelatin and human extracellular matrix (hECM) to print human HepaRG liver cells with a pneumatic extrusion printer. The resulting tissue model was tested for its suitability for the study of transduction by an adeno-associated virus (AAV) vector and infection with human adenovirus 5 (hAdV5). We found supplementation of the basic alginate/gelatin bioink with 0.5 and 1 mg/mL hECM provides desirable properties for the printing process, the stability of the printed constructs, and the viability and metabolic functions of the printed HepaRG cells. The tissue models were efficiently transduced by AAV vectors of serotype 6, which successfully silenced an endogenous target (cyclophilin B) by means of RNA interference. Furthermore, the printed 3D model supported efficient adenoviral replication making it suitable to study virus biology and develop new antiviral compounds. We consider the approach described here paradigmatic for the development of 3D tissue models for studies including viral vectors and infectious viruses.
Issue Date: 12-Oct-2018
Date Available: 5-Nov-2018
DDC Class: 570 Biowissenschaften; Biologie
Subject(s): adeno-associated virus
extracellular matrix
organ models
gene silencing
Sponsor/Funder: DFG, TH 662/19-1, Open Access Publizieren 2017 - 2018 / Technische Universität Berlin
Journal Title: International Journal of Molecular Sciences
Publisher: MDPI
Publisher Place: Basel
Volume: 19
Issue: 10
Article Number: 3129
Publisher DOI: 10.3390/ijms19103129
EISSN: 1422-0067
Appears in Collections:FG Angewandte Biochemie » Publications

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