PMID- 28559920
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200929
IS  - 1745-6673 (Print)
IS  - 1745-6673 (Electronic)
IS  - 1745-6673 (Linking)
VI  - 12
DP  - 2017
TI  - Assessment of long-term cultivated human precision-cut lung slices as an ex vivo 
      system for evaluation of chronic cytotoxicity and functionality.
PG  - 13
LID - 10.1186/s12995-017-0158-5 [doi]
LID - 13
AB  - 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 (EC(50)1d = 4 x 10(-8) M vs. EC(50)15d = 4 x 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-alpha 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.
FAU - Neuhaus, Vanessa
AU  - Neuhaus V
AD  - Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover, Germany, 
      Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), 
      Member of the German Centre for Lung Research (DZL), Member of the REBIRTH 
      Cluster of Excellence, Hanover, Germany. ISNI: 0000 0000 9191 9864. GRID: 
      grid.418009.4
FAU - Schaudien, Dirk
AU  - Schaudien D
AD  - Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover, Germany, 
      Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), 
      Member of the German Centre for Lung Research (DZL), Member of the REBIRTH 
      Cluster of Excellence, Hanover, Germany. ISNI: 0000 0000 9191 9864. GRID: 
      grid.418009.4
FAU - Golovina, Tatiana
AU  - Golovina T
AD  - Fraunhofer USA Center for Molecular Biotechnology, Newark, DE USA. GRID: 
      grid.418018.4
FAU - Temann, Ulla-Angela
AU  - Temann UA
AD  - Fraunhofer USA Center for Molecular Biotechnology, Newark, DE USA. GRID: 
      grid.418018.4
FAU - Thompson, Carolann
AU  - Thompson C
AD  - Fraunhofer USA Center for Molecular Biotechnology, Newark, DE USA. GRID: 
      grid.418018.4
FAU - Lippmann, Torsten
AU  - Lippmann T
AD  - Institute for Pathology, Hannover Medical School, Hanover, Germany, Biomedical 
      Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of 
      the German Centre for Lung Research (DZL), Hanover, Germany. ISNI: 0000 0000 9529 
      9877. GRID: grid.10423.34
FAU - Bersch, Claus
AU  - Bersch C
AD  - Klinikum Region Hannover (KRH), Institute of Pathology, Hanover, Germany. ISNI: 
      0000 0000 9597 1037. GRID: grid.412811.f
FAU - Pfennig, Olaf
AU  - Pfennig O
AD  - Klinikum Region Hannover (KRH), Institute of Pathology, Hanover, Germany. ISNI: 
      0000 0000 9597 1037. GRID: grid.412811.f
FAU - Jonigk, Danny
AU  - Jonigk D
AD  - Institute for Pathology, Hannover Medical School, Hanover, Germany, Biomedical 
      Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of 
      the German Centre for Lung Research (DZL), Hanover, Germany. ISNI: 0000 0000 9529 
      9877. GRID: grid.10423.34
FAU - Braubach, Peter
AU  - Braubach P
AD  - Institute for Pathology, Hannover Medical School, Hanover, Germany, Biomedical 
      Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of 
      the German Centre for Lung Research (DZL), Hanover, Germany. ISNI: 0000 0000 9529 
      9877. GRID: grid.10423.34
FAU - Fieguth, Hans-Gerd
AU  - Fieguth HG
AD  - Klinikum Region Hannover (KRH), Division of Thoracic and Vascular surgery, 
      Hanover, Germany. ISNI: 0000 0000 9597 1037. GRID: grid.412811.f
FAU - Warnecke, Gregor
AU  - Warnecke G
AD  - Division of Cardiac, Thoracic, Transplantation, and Vascular Surgery, Hannover 
      Medical School, Hanover, Germany, Biomedical Research in Endstage and Obstructive 
      Lung Disease Hannover (BREATH), Member of the German Centre for Lung Research 
      (DZL), Hanover, Germany. ISNI: 0000 0000 9529 9877. GRID: grid.10423.34
FAU - Yusibov, Vidadi
AU  - Yusibov V
AD  - Fraunhofer USA Center for Molecular Biotechnology, Newark, DE USA. GRID: 
      grid.418018.4
FAU - Sewald, Katherina
AU  - Sewald K
AD  - Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover, Germany, 
      Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), 
      Member of the German Centre for Lung Research (DZL), Member of the REBIRTH 
      Cluster of Excellence, Hanover, Germany. ISNI: 0000 0000 9191 9864. GRID: 
      grid.418009.4
FAU - Braun, Armin
AU  - Braun A
AD  - Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover, Germany, 
      Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), 
      Member of the German Centre for Lung Research (DZL), Member of the REBIRTH 
      Cluster of Excellence, Hanover, Germany. ISNI: 0000 0000 9191 9864. GRID: 
      grid.418009.4
AD  - Institute of Immunology, Hannover Medical School, Hanover, Germany. ISNI: 0000 
      0000 9529 9877. GRID: grid.10423.34
LA  - eng
PT  - Journal Article
DEP - 20170526
PL  - England
TA  - J Occup Med Toxicol
JT  - Journal of occupational medicine and toxicology (London, England)
JID - 101245790
PMC - PMC5446749
OTO - NOTNLM
OT  - Bronchoconstriction
OT  - Cytokines
OT  - Cytotoxicity
OT  - Human
OT  - Long-term cultivation
OT  - PCLS
OT  - Precision-cut lung slices
EDAT- 2017/06/01 06:00
MHDA- 2017/06/01 06:01
PMCR- 2017/05/26
CRDT- 2017/06/01 06:00
PHST- 2016/09/30 00:00 [received]
PHST- 2017/05/11 00:00 [accepted]
PHST- 2017/06/01 06:00 [entrez]
PHST- 2017/06/01 06:00 [pubmed]
PHST- 2017/06/01 06:01 [medline]
PHST- 2017/05/26 00:00 [pmc-release]
AID - 158 [pii]
AID - 10.1186/s12995-017-0158-5 [doi]
PST - epublish
SO  - J Occup Med Toxicol. 2017 May 26;12:13. doi: 10.1186/s12995-017-0158-5. 
      eCollection 2017.