An in vitro osteosarcoma 3D microtissue model for drug development

Fuchs, Bruno; Rimann, Markus; Graf-Hausner, Ursula; Laternser, Sandra; Kelm, Jens; Gvozdenovic, Ana; Muff, Roman

doi:10.1016/j.jbiotec.2014.09.005

Publication type:	Article in scientific journal
Type of review:	Peer review (publication)
Title:	An in vitro osteosarcoma 3D microtissue model for drug development
Authors:	Fuchs, Bruno Rimann, Markus Graf-Hausner, Ursula Laternser, Sandra Kelm, Jens Gvozdenovic, Ana Muff, Roman
DOI:	10.1016/j.jbiotec.2014.09.005
Published in:	Journal of Biotechnology
Volume(Issue):	189
Page(s):	129
Pages to:	135
Issue Date:	2014
Publisher / Ed. Institution:	Elsevier
ISSN:	0168-1656 1873-4863
Language:	English
Subjects:	3D cell culture; Drug Development; Osteosarcoma; Microtissues
Subject (DDC):	615: Pharmacology and therapeutics
Abstract:	Osteosarcoma (OS) is the most common primary malignant bone tumour in children and adolescents. Therapy today includes surgical removal of the tumour and neoadjuvant and adjuvant chemotherapy. The 5-year survival rates for patients with localised disease are between 50 and 70%, but in patients with metastases the prognosis remains poor (∼20%). The aim of this study was the development of a biological relevant OS 3D microtissue model, which is suitable for drug development. Microtissues were formed by the hanging drop method with the established OS cell lines SaOS-2, HOS and MG-63, as well as with cells derived from osteoblastic and chondroblastic OS patient material. Histological characterisation of the microtissues with H/E- and Ki-67-(proliferation), as well as apoptosis staining (TUNEL) revealed the inherent histological heterogeneity of OS. Microtissues from SaOS-2 and HOS cell lines were exposed to doxorubicin, cisplatin, taurolidine, pemetrexed and taxol and the viability was assessed by the CellTiter-GLO® Luminescent Cell Viability Assay. The obtained IC50-values for 3D cultures were all higher (1.7 to >16,000-fold) when compared to corresponding cells grown in 2D monolayer culture, except for pemetrexed that was inactive in 2D and 3D cultures. Doxorubicin did not affect the viability of chondroblastic monolayer cultures whereas on 3D microtissues an IC50-value of 2.3 μM was obtained. The 3D microtissues reflect the tissue heterogeneity of OS and are potential suitable tools for drug development towards personalised medicine.
URI:	https://digitalcollection.zhaw.ch/handle/11475/1573
Fulltext version:	Published version
License (according to publishing contract):	Licence according to publishing contract
Departement:	Life Sciences and Facility Management
Organisational Unit:	Institute of Chemistry and Biotechnology (ICBT)
Appears in collections:	Publikationen Life Sciences und Facility Management

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Fuchs, B., Rimann, M., Graf-Hausner, U., Laternser, S., Kelm, J., Gvozdenovic, A., & Muff, R. (2014). An in vitro osteosarcoma 3D microtissue model for drug development. Journal of Biotechnology, 189, 129–135. https://doi.org/10.1016/j.jbiotec.2014.09.005

Fuchs, B. et al. (2014) ‘An in vitro osteosarcoma 3D microtissue model for drug development’, Journal of Biotechnology, 189, pp. 129–135. Available at: https://doi.org/10.1016/j.jbiotec.2014.09.005.

B. Fuchs et al., “An in vitro osteosarcoma 3D microtissue model for drug development,” Journal of Biotechnology, vol. 189, pp. 129–135, 2014, doi: 10.1016/j.jbiotec.2014.09.005.

FUCHS, Bruno, Markus RIMANN, Ursula GRAF-HAUSNER, Sandra LATERNSER, Jens KELM, Ana GVOZDENOVIC und Roman MUFF, 2014. An in vitro osteosarcoma 3D microtissue model for drug development. Journal of Biotechnology. 2014. Bd. 189, S. 129–135. DOI 10.1016/j.jbiotec.2014.09.005

Fuchs, Bruno, Markus Rimann, Ursula Graf-Hausner, Sandra Laternser, Jens Kelm, Ana Gvozdenovic, and Roman Muff. 2014. “An in Vitro Osteosarcoma 3D Microtissue Model for Drug Development.” Journal of Biotechnology 189: 129–35. https://doi.org/10.1016/j.jbiotec.2014.09.005.

Fuchs, Bruno, et al. “An in Vitro Osteosarcoma 3D Microtissue Model for Drug Development.” Journal of Biotechnology, vol. 189, 2014, pp. 129–35, https://doi.org/10.1016/j.jbiotec.2014.09.005.