PMID- 36127699
OWN - NLM
STAT- MEDLINE
DCOM- 20220923
LR  - 20221003
IS  - 1465-993X (Electronic)
IS  - 1465-9921 (Print)
IS  - 1465-9921 (Linking)
VI  - 23
IP  - 1
DP  - 2022 Sep 20
TI  - Functional changes in long-term incubated rat precision-cut lung slices.
PG  - 261
LID - 10.1186/s12931-022-02169-5 [doi]
LID - 261
AB  - BACKGROUND: Respiratory diseases represent a global health burden. Because 
      research on therapeutic strategies of airway diseases is essential, the technique 
      of precision-cut lung slices (PCLS) has been developed and widely studied. PCLS 
      are an alternative ex vivo model and have the potential to replace and reduce in 
      vivo animal models. So far, the majority of studies was conducted with short-term 
      cultivated PCLS (</= 72 h). As there is large interest in research of chronic 
      diseases and chronic toxicity, feasibility of cultivating human PCLS long-term 
      over 2 weeks and recently over 4 weeks was investigated by another research group 
      with successful results. Our aim was to establish a model of long-term cultivated 
      rat PCLS over a period of 29 days. METHODS: Rat PCLS were cultured for 29 days 
      and analysed regarding viability, histopathology, reactivity and gene expression 
      at different time points during cultivation. RESULTS: Cultivation of rat PCLS 
      over a 29-day time period was successful with sustained viability. Furthermore, 
      the ability of bronchoconstriction was maintained between 13 and 25 days, 
      depending on the mediator. However, reduced relaxation, altered sensitivity and 
      increased respiratory tone were observed. Regarding transcription, alteration in 
      gene expression pattern of the investigated target genes was ascertained during 
      long-term cultivation with mixed results. Furthermore, the preparation of PCLS 
      seems to influence messenger ribonucleic acid (mRNA) expression of most target 
      genes. Moreover, the addition of fetal bovine serum (FBS) to the culture medium 
      did not improve viability of PCLS. In contrast to medium without FBS, FBS seems 
      to affect measurements and resulted in marked cellular changes of metaplastic 
      and/or regenerative origin. CONCLUSIONS: Overall, a model of long-term cultivated 
      rat PCLS which stays viable for 29 days and reactive for at least 13 days could 
      be established. Before long-term cultivated PCLS can be used for in-depth study 
      of chronic diseases and chronic toxicity, further investigations have to be made.
CI  - (c) 2022. The Author(s).
FAU - Nussbaum, Sarah Marie
AU  - Nussbaum SM
AD  - Institute of Pharmacology and Toxicology, Medical Faculty, RWTH Aachen 
      University, Wendlingweg 2, 52074, Aachen, Germany.
FAU - Krabbe, Julia
AU  - Krabbe J
AD  - Institute of Occupational, Social and Environmental Medicine, Medical Faculty, 
      RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany.
FAU - Boll, Svenja
AU  - Boll S
AD  - Department of Pediatrics, Medical Faculty, RWTH Aachen University, University 
      Hospital Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany.
FAU - Babendreyer, Aaron
AU  - Babendreyer A
AD  - Institute of Molecular Pharmacology, Medical Faculty, RWTH Aachen University, 
      Wendlingweg 2, 52074, Aachen, Germany.
FAU - Martin, Christian
AU  - Martin C
AD  - Institute of Pharmacology and Toxicology, Medical Faculty, RWTH Aachen 
      University, Wendlingweg 2, 52074, Aachen, Germany. chmartin@ukaachen.de.
LA  - eng
PT  - Journal Article
DEP - 20220920
PL  - England
TA  - Respir Res
JT  - Respiratory research
JID - 101090633
RN  - 0 (RNA, Messenger)
RN  - 27432CM55Q (Serum Albumin, Bovine)
RN  - 63231-63-0 (RNA)
SB  - IM
MH  - Animals
MH  - *Bronchoconstriction
MH  - Humans
MH  - *Lung/pathology
MH  - RNA
MH  - RNA, Messenger
MH  - Rats
MH  - Serum Albumin, Bovine
MH  - Tissue Culture Techniques
PMC - PMC9490993
OTO - NOTNLM
OT  - Bronchoconstriction
OT  - FBS
OT  - Fetal bovine serum
OT  - Gene expression
OT  - Histopathology
OT  - Long-term incubation
OT  - PCLS
OT  - Precision-cut lung slices
OT  - Rat
OT  - Viability
COIS- The authors declare that they have no competing interests.
EDAT- 2022/09/21 06:00
MHDA- 2022/09/24 06:00
PMCR- 2022/09/20
CRDT- 2022/09/20 23:39
PHST- 2022/02/15 00:00 [received]
PHST- 2022/09/02 00:00 [accepted]
PHST- 2022/09/20 23:39 [entrez]
PHST- 2022/09/21 06:00 [pubmed]
PHST- 2022/09/24 06:00 [medline]
PHST- 2022/09/20 00:00 [pmc-release]
AID - 10.1186/s12931-022-02169-5 [pii]
AID - 2169 [pii]
AID - 10.1186/s12931-022-02169-5 [doi]
PST - epublish
SO  - Respir Res. 2022 Sep 20;23(1):261. doi: 10.1186/s12931-022-02169-5.