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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-12

AUTHORS

Vanessa Neuhaus, Dirk Schaudien, Tatiana Golovina, Ulla-Angela Temann, Carolann Thompson, Torsten Lippmann, Claus Bersch, Olaf Pfennig, Danny Jonigk, Peter Braubach, Hans-Gerd Fieguth, Gregor Warnecke, Vidadi Yusibov, Katherina Sewald, Armin Braun

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 (≤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 whole period of cultivation, though with decreased sensitivity (EC501d = 4 × 10-8 M vs. EC5015d = 4 × 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. More... »

PAGES

13

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s12995-017-0158-5

DOI

http://dx.doi.org/10.1186/s12995-017-0158-5

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1085598091

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/28559920


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    "description": "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 (\u226472\u00a0h), 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\u00a0days.\nMETHODS: PCLS were cultured for 15\u00a0days and various parameters were assessed at different time points.\nRESULTS: Structural integrity and viability of cultured PCLS remained constant for 15\u00a0days. Moreover, bronchoconstriction was inducible over the whole period of cultivation, though with decreased sensitivity (EC501d\u00a0=\u00a04\u00a0\u00d7\u00a010-8\u00a0M vs. EC5015d\u00a0=\u00a04\u00a0\u00d7\u00a010-6\u00a0M) and reduced maximum of initial airway area (1d\u00a0=\u00a00.5% vs. 15d\u00a0=\u00a018.7%). In contrast, even though still clearly inducible compared to medium control, LPS-induced TNF-\u03b1 secretion decreased significantly from day 1 to day 15 of culture.\nCONCLUSIONS: 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.", 
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278 rdf:type schema:Organization
279 https://www.grid.ac/institutes/grid.418018.4 schema:alternateName Center for Molecular Biotechnology
280 schema:name Fraunhofer USA Center for Molecular Biotechnology, Newark, DE, USA
281 rdf:type schema:Organization
 




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