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Use of rat precision-cut lung slices for long-term functional evaluation

: Neuhaus, Vanessa; Braun, Armin; Sewald, Katherina

The Toxicologist 53 (2014), No.1, pp.273, PS 1051
ISSN: 0731-9193
Society of Toxicology (Annual Meeting) <53, 2014, Phoenix/Ariz.>
Fraunhofer ITEM ()

The need of alternative methods for animal studies to investigate basic inflammatory mechanism and to test toxicological potential of new substances has been increased during the last decades. Precision-cut lung slices (PCLS) have been proven to be a valuable alternative for mammalian in vivo studies reflecting relevant factors of the respiratory tract in accordance with the three R principles. However PCLS have been used mostly for short-term cultivation (<= 72h) only, which limits their use to certain questions. When it comes to analyses of slowly metabolized chemicals and to repeated application of compounds, the long-term cultivation of PCLS might be utterly important. In this study viability and maintenance of structure and functionality of long-term cultured (>= 14 days) rat PCLS was investigated.
Rat PCLS were cultured for 15 days. Readout parameters for vitality (WST-1 assay) and functionality were assessed at different time periods. Ability to secret the pro-inflammatory cytokine Tumor necrosis factor alpha (TNF-
Overall these results show that a general long-term cultivation of rat PCLS with a good preservation of the viability is feasible. However, the decreased functionality indicates that some cellular alterations have been taken place. This implies that the long-term cultivation of rat PCLS is feasible for bronchoconstriction studies and toxicity assays, but unusable yet for induced cytokine secretion.