Novel drug
screening platform for lung fibrosis-LSC system
Lung disease, such as pulmonary fibrosis, is widely prevalent with no effective
cure. Therapeutic approaches to lung fibrosis are challenging owing to lack of
effective experimental models for either mechanistic studies or for drug
screening purposes.
The one example often seen in scientific literature is the bleomycin-induced
animal model. In this experimental model, pulmonary inflammation is severely
involved in the fibrotic pathogenesis which seems to be different from human
idiopathic pulmonary fibrosis. Animal models are thus relatively impractical
for drug screening. Cell culture systems have been applied for drug screening
purpose. However, they do not reflect the complexity of this disease in terms
of cell-cell and cell-matrix interactions in a three dimensional alveolar
structure.
Considering the complexity of fibrogenic process and the high cost of drug
development, Bio S&T sought to establish an alternative model incorporating
low cost and higher efficiency for drug screening purposes. Bio S&T has
successfully established an ex vivo rat lung slice culture (LSC) system
which bridges the advantages of in vivo model with the ease of in vitro
techniques.
Bio S&T has successfully established an ex vivo
rat lung slice culture (LSC) system which bridges
the advantages of in vivo model
with the ease of in vitro techniques.
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Extensive experiments have shown that the system is highly consistent and
stable on induction of collagen formation. Early alveolar fibrotic features can
be induced within a much shorter time (days) compared to the animal model.
Increasing collagen content in the lung slices can be detected by quantitative
analysis of hydroxyproline (see Chart 1). Expression of fibrosis-related genes
expression can also be observed via PCR (see Figure 1 ).
Chart
1: Hydroxyproline (ug) per mg of dry lung slice tissue (average results
are shown with standard devations for 4 independent tests perfomed in
triplicate)

Figure 1. Expression of fibrosis-related genes in non-induced and
induced cultured lung slices (days 2, 5 and 8
shown).


The LSC platform is powerful in that it allows for compound
screening with the relevant and appropriate controls in a sequential manner,
with the concomitant opportunity to conduct tissue morphology analyses.
All these attributes make LSC the best choice available for
effective compound screening in relation to control of pulmonary fibrosis.
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