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Sci Rep. 2017 Nov 3;7(1):14490. doi: 10.1038/s41598-017-12683-y.

Monitoring and manipulating cellular crosstalk during kidney fibrosis inside a 3D in vitro co-culture.

Author information

1
Department of Biosystems Science and Engineering (D-BSSE), Eidgenössische Technische Hochschule (ETH) Zurich, Mattenstrasse 26, 4058, Basel, Switzerland.
2
Roche Pharmaceutical Research and Early Development (pRED), Roche Innovation Center Basel, 4070, Basel, Switzerland.
3
Department of Surgical Research, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland.
4
Institute for Regenerative Medicine (IREM), Wyss Translational Center Zurich, University of Zurich, Wagistrasse 12, 8952, Schlieren, Switzerland.
5
Institute for Regenerative Medicine (IREM), University of Zurich, Wagistrasse 12, 8952, Schlieren, Switzerland.
6
University Heart Center, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland.
7
Wyss Translational Center Zurich, Moussonstrasse 13, 8044, Zurich, Switzerland.
8
Department of Pathology, University Hospital of Geneva, Geneva, Switzerland.
9
Roche Pharmaceutical Research and Early Development (pRED), Roche Innovation Center Basel, 4070, Basel, Switzerland. marco.prunotto@roche.com.
10
Department of Biosystems Science and Engineering (D-BSSE), Eidgenössische Technische Hochschule (ETH) Zurich, Mattenstrasse 26, 4058, Basel, Switzerland. periklis.pantazis@bsse.ethz.ch.

Abstract

In pharmacological research the development of promising lead compounds requires a detailed understanding of the dynamics of disease progression. However, for many diseases, such as kidney fibrosis, gaining such understanding requires complex real-time, multi-dimensional analysis of diseased and healthy tissue. To allow for such studies with increased throughput we established a dextran hydrogel-based in vitro 3D co-culture as a disease model for kidney fibrosis aimed at the discovery of compounds modulating the epithelial/mesenchymal crosstalk. This platform mimics a simplified pathological renal microenvironment at the interface between tubular epithelial cells and surrounding quiescent fibroblasts. We combined this 3D technology with epithelial reporter cell lines expressing fluorescent biomarkers in order to visualize pathophysiological cell state changes resulting from toxin-mediated chemical injury. Epithelial cell damage onset was robustly detected by image-based monitoring, and injured epithelial spheroids induced myofibroblast differentiation of co-cultured quiescent human fibroblasts. The presented 3D co-culture system therefore provides a unique model system for screening of novel therapeutic molecules capable to interfere and modulate the dialogue between epithelial and mesenchymal cells.

PMID:
29101326
PMCID:
PMC5670242
DOI:
10.1038/s41598-017-12683-y
[Indexed for MEDLINE]
Free PMC Article

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