Generation of a 3D liver model comprising human extracellular matrix in an alginate/gelatin-based bioink by extrusion bioprinting for infection and transduction studies

Publikation: Beitrag in FachzeitschriftArtikelForschungPeer-Review

Autoren

  • Thomas Hiller
  • Johanna Berg
  • Laura Elomaa
  • Viola Röhrs
  • Imran Ullah
  • Katrin Schaar
  • Ann Christin Dietrich
  • Munir A. Al-Zeer
  • Andreas Kurtz
  • Andreas C. Hocke
  • Stefan Hippenstiel
  • Henry Fechner
  • Marie Weinhart
  • Jens Kurreck

Externe Organisationen

  • Technische Universität Berlin
  • Freie Universität Berlin (FU Berlin)
  • Charité - Universitätsmedizin Berlin
Forschungs-netzwerk anzeigen

Details

OriginalspracheEnglisch
Aufsatznummer3129
FachzeitschriftInternational Journal of Molecular Sciences
Jahrgang19
Ausgabenummer10
PublikationsstatusVeröffentlicht - 12 Okt. 2018
Extern publiziertJa

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.

ASJC Scopus Sachgebiete

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Generation of a 3D liver model comprising human extracellular matrix in an alginate/gelatin-based bioink by extrusion bioprinting for infection and transduction studies. / Hiller, Thomas; Berg, Johanna; Elomaa, Laura et al.
in: International Journal of Molecular Sciences, Jahrgang 19, Nr. 10, 3129, 12.10.2018.

Publikation: Beitrag in FachzeitschriftArtikelForschungPeer-Review

Hiller, T, Berg, J, Elomaa, L, Röhrs, V, Ullah, I, Schaar, K, Dietrich, AC, Al-Zeer, MA, Kurtz, A, Hocke, AC, Hippenstiel, S, Fechner, H, Weinhart, M & Kurreck, J 2018, 'Generation of a 3D liver model comprising human extracellular matrix in an alginate/gelatin-based bioink by extrusion bioprinting for infection and transduction studies', International Journal of Molecular Sciences, Jg. 19, Nr. 10, 3129. https://doi.org/10.3390/ijms19103129
Hiller, T., Berg, J., Elomaa, L., Röhrs, V., Ullah, I., Schaar, K., Dietrich, A. C., Al-Zeer, M. A., Kurtz, A., Hocke, A. C., Hippenstiel, S., Fechner, H., Weinhart, M., & Kurreck, J. (2018). Generation of a 3D liver model comprising human extracellular matrix in an alginate/gelatin-based bioink by extrusion bioprinting for infection and transduction studies. International Journal of Molecular Sciences, 19(10), Artikel 3129. https://doi.org/10.3390/ijms19103129
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@article{18d6bbf49b6643118ffb136627f1363b,
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",
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.",
keywords = "Adeno-associated virus, Adenovirus, Bioprinting, Extracellular matrix, Gene silencing, HepaRG, Infection, Liver, Organ models, Transduction",
author = "Thomas Hiller and Johanna Berg and Laura Elomaa and Viola R{\"o}hrs and Imran Ullah and Katrin Schaar and Dietrich, {Ann Christin} and Al-Zeer, {Munir A.} and Andreas Kurtz and Hocke, {Andreas C.} and Stefan Hippenstiel and Henry Fechner and Marie Weinhart and Jens Kurreck",
note = "Funding Information: Funding: This research was funded by the Stiftung zur F{\"o}rderung der Erforschung von Ersatz-und Erg{\"a}nzungsmethoden zur Einschr{\"a}nkung von Tierversuchen (SET) and the Bundesinstitut f{\"u}r Risikobewertung, grant number 1328-568 to J.K. as well the Deutsche Forschungsgemeinschaft, grants DFG-SFB-TR84 B06 (to A.C.H and S.H.) and Z01 (to A.C.H.). We acknowledge support by the German Research Foundation and the Open Access Publication Funds of TU Berlin. Publisher Copyright: {\textcopyright} 2018 by the authors. Licensee MDPI, Basel, Switzerland.",
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journal = "International Journal of Molecular Sciences",
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Download

TY - JOUR

T1 - Generation of a 3D liver model comprising human extracellular matrix in an alginate/gelatin-based bioink by extrusion bioprinting for infection and transduction studies

AU - Hiller, Thomas

AU - Berg, Johanna

AU - Elomaa, Laura

AU - Röhrs, Viola

AU - Ullah, Imran

AU - Schaar, Katrin

AU - Dietrich, Ann Christin

AU - Al-Zeer, Munir A.

AU - Kurtz, Andreas

AU - Hocke, Andreas C.

AU - Hippenstiel, Stefan

AU - Fechner, Henry

AU - Weinhart, Marie

AU - Kurreck, Jens

N1 - Funding Information: Funding: This research was funded by the Stiftung zur Förderung der Erforschung von Ersatz-und Ergänzungsmethoden zur Einschränkung von Tierversuchen (SET) and the Bundesinstitut für Risikobewertung, grant number 1328-568 to J.K. as well the Deutsche Forschungsgemeinschaft, grants DFG-SFB-TR84 B06 (to A.C.H and S.H.) and Z01 (to A.C.H.). We acknowledge support by the German Research Foundation and the Open Access Publication Funds of TU Berlin. Publisher Copyright: © 2018 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2018/10/12

Y1 - 2018/10/12

N2 - 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.

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KW - Adenovirus

KW - Bioprinting

KW - Extracellular matrix

KW - Gene silencing

KW - HepaRG

KW - Infection

KW - Liver

KW - Organ models

KW - Transduction

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U2 - 10.3390/ijms19103129

DO - 10.3390/ijms19103129

M3 - Article

C2 - 30321994

AN - SCOPUS:85054896456

VL - 19

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

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