PMID- 34767811
OWN - NLM
STAT- MEDLINE
DCOM- 20220302
LR  - 20220308
IS  - 1525-2191 (Electronic)
IS  - 0002-9440 (Print)
IS  - 0002-9440 (Linking)
VI  - 192
IP  - 2
DP  - 2022 Feb
TI  - The Challenge of Long-Term Cultivation of Human Precision-Cut Lung Slices.
PG  - 239-253
LID - S0002-9440(21)00481-8 [pii]
LID - 10.1016/j.ajpath.2021.10.020 [doi]
AB  - Human precision-cut lung slices (PCLS) have proven to be an invaluable tool for 
      numerous toxicologic, pharmacologic, and immunologic studies. Although a 
      cultivation period of <1 week is sufficient for most studies, modeling of complex 
      disease mechanisms and investigating effects of long-term exposure to certain 
      substances require cultivation periods that are much longer. So far, data 
      regarding tissue integrity of long-term cultivated PCLS are incomplete. More than 
      1500 human PCLS from 16 different donors were cultivated under standardized, 
      serum-free conditions for up to 28 days and the viability, tissue integrity, and 
      the transcriptome was assessed in great detail. Even though viability of PCLS was 
      well preserved during long-term cultivation, a continuous loss of cells was 
      observed. Although the bronchial epithelium was well preserved throughout 
      cultivation, the alveolar integrity was preserved for about 2 weeks, and the 
      vasculatory system experienced significant loss of integrity within the first 
      week. Furthermore, ciliary beat in the small airways gradually decreased after 1 
      week. Interestingly, keratinizing squamous metaplasia of the alveolar epithelium 
      with significantly increasing manifestation were found over time. Transcriptome 
      analysis revealed a significantly increased immune response and significantly 
      decreased metabolic activity within the first 24 hours after PCLS generation. 
      Overall, this study provides a comprehensive overview of histomorphologic and 
      pathologic changes during long-term cultivation of PCLS.
CI  - Copyright (c) 2022 American Society for Investigative Pathology. Published by 
      Elsevier Inc. All rights reserved.
FAU - Preuss, Eike B
AU  - Preuss EB
AD  - Institute of Pathology, Lung Research Group, Hannover Medical School, Hannover, 
      Germany. Electronic address: preuss.eike@mh-hannover.de.
FAU - Schubert, Stephanie
AU  - Schubert S
AD  - Institute of Pathology, Lung Research Group, Hannover Medical School, Hannover, 
      Germany.
FAU - Werlein, Christopher
AU  - Werlein C
AD  - Institute of Pathology, Lung Research Group, Hannover Medical School, Hannover, 
      Germany.
FAU - Stark, Helge
AU  - Stark H
AD  - Institute of Pathology, Lung Research Group, Hannover Medical School, Hannover, 
      Germany.
FAU - Braubach, Peter
AU  - Braubach P
AD  - Institute of Pathology, Lung Research Group, Hannover Medical School, Hannover, 
      Germany.
FAU - Hofer, Anne
AU  - Hofer A
AD  - Institute of Pathology, Lung Research Group, Hannover Medical School, Hannover, 
      Germany.
FAU - Plucinski, Edith K J
AU  - Plucinski EKJ
AD  - Institute of Pathology, Lung Research Group, Hannover Medical School, Hannover, 
      Germany.
FAU - Shah, Harshit R
AU  - Shah HR
AD  - Institute of Pathology, Lung Research Group, Hannover Medical School, Hannover, 
      Germany.
FAU - Geffers, Robert
AU  - Geffers R
AD  - Genome Analytics, Helmholtz Centre for Infection Research, Braunschweig, Germany.
FAU - Sewald, Katherina
AU  - Sewald K
AD  - Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover, Germany.
FAU - Braun, Armin
AU  - Braun A
AD  - Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover, Germany.
FAU - Jonigk, Danny D
AU  - Jonigk DD
AD  - Institute of Pathology, Lung Research Group, Hannover Medical School, Hannover, 
      Germany.
FAU - Kuhnel, Mark P
AU  - Kuhnel MP
AD  - Institute of Pathology, Lung Research Group, Hannover Medical School, Hannover, 
      Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20211110
PL  - United States
TA  - Am J Pathol
JT  - The American journal of pathology
JID - 0370502
SB  - IM
MH  - Adult
MH  - Aged
MH  - Female
MH  - Humans
MH  - Lung/*metabolism/pathology
MH  - Male
MH  - Middle Aged
MH  - Organ Culture Techniques
MH  - Time Factors
PMC - PMC8891143
EDAT- 2021/11/13 06:00
MHDA- 2022/03/03 06:00
PMCR- 2022/02/01
CRDT- 2021/11/12 20:13
PHST- 2021/08/19 00:00 [received]
PHST- 2021/10/10 00:00 [revised]
PHST- 2021/10/19 00:00 [accepted]
PHST- 2021/11/13 06:00 [pubmed]
PHST- 2022/03/03 06:00 [medline]
PHST- 2021/11/12 20:13 [entrez]
PHST- 2022/02/01 00:00 [pmc-release]
AID - S0002-9440(21)00481-8 [pii]
AID - 10.1016/j.ajpath.2021.10.020 [doi]
PST - ppublish
SO  - Am J Pathol. 2022 Feb;192(2):239-253. doi: 10.1016/j.ajpath.2021.10.020. Epub 
      2021 Nov 10.