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2017 ; 7
(1
): 14490
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Monitoring and manipulating cellular crosstalk during kidney fibrosis inside a 3D
in vitro co-culture
#MMPMID29101326
Nugraha B
; Mohr MA
; Ponti A
; Emmert MY
; Weibel F
; Hoerstrup SP
; Moll S
; Certa U
; Prunotto M
; Pantazis P
Sci Rep
2017[Nov]; 7
(1
): 14490
PMID29101326
show ga
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.
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