Details
| Original language | English |
|---|---|
| Article number | 3129 |
| Journal | International Journal of Molecular Sciences |
| Volume | 19 |
| Issue number | 10 |
| Publication status | Published - 12 Oct 2018 |
| Externally published | Yes |
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
ASJC Scopus subject areas
- Chemical Engineering(all)
- Catalysis
- Biochemistry, Genetics and Molecular Biology(all)
- Molecular Biology
- Chemistry(all)
- Spectroscopy
- Computer Science(all)
- Computer Science Applications
- Chemistry(all)
- Physical and Theoretical Chemistry
- Chemistry(all)
- Organic Chemistry
- Chemistry(all)
- Inorganic Chemistry
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In: International Journal of Molecular Sciences, Vol. 19, No. 10, 3129, 12.10.2018.
Research output: Contribution to journal › Article › Research › peer review
}
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.
AB - 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.
KW - Adeno-associated virus
KW - Adenovirus
KW - Bioprinting
KW - Extracellular matrix
KW - Gene silencing
KW - HepaRG
KW - Infection
KW - Liver
KW - Organ models
KW - Transduction
UR - http://www.scopus.com/inward/record.url?scp=85054896456&partnerID=8YFLogxK
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
IS - 10
M1 - 3129
ER -