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Assessment of long-term cultivated human precision-cut lung slices as an ex vivo system for evaluation of chronic cytotoxicity and functionality

 
: Neuhaus, V.; Schaudien, D.; Golovina, T.; Temann, U.-A.; Thompson, C.; Lippmann, T.; Bersch, C.; Pfennig, O.; Jonigk, D.; Braubach, P.; Fieguth, H.-G.; Warnecke, G.; Yusibov, V.; Sewald, K.; Braun, A.

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Journal of occupational medicine and toxicology. Online journal 12 (2017), No.1, Art. 13, 8 pp.
http://www.occup-med.com/
ISSN: 1745-6673
English
Journal Article, Electronic Publication
Fraunhofer ITEM ()

Abstract
Background: Investigation of basic chronic inflammatory mechanisms and development of new therapeutics targeting the respiratory tract requires appropriate testing systems, including those to monitor long- persistence. Human precision-cut lung slices (PCLS) have been demonstrated to mimic the human respiratory tract and have potential of an alternative, ex-vivo system to replace or augment in-vitro testing and animal models. So far, most research on PCLS has been conducted for short cultivation periods (â¤72 h), while analyses of slowly metabolized therapeutics require long-term survival of PCLS in culture. In the present study, we evaluated viability, physiology and structural integrity of PCLS cultured for up to 15 days. Methods: PCLS were cultured for 15 days and various parameters were assessed at different time points. Results: Structural integrity and viability of cultured PCLS remained constant for 15 days. Moreover, bronchoconstriction was inducible over the wh ole period of cultivation, though with decreased sensitivity (EC501d = 4 à 10-8 M vs. EC5015d = 4 à 10-6 M) and reduced maximum of initial airway area (1d = 0.5% vs. 15d = 18.7%). In contrast, even though still clearly inducible compared to medium control, LPS-induced TNF-α secretion decreased significantly from day 1 to day 15 of culture. Conclusions: Overall, though long-term cultivation of PCLS need further investigation for cytokine secretion, possibly on a cellular level, PCLS are feasible for bronchoconstriction studies and toxicity assays.

: http://publica.fraunhofer.de/documents/N-456014.html