PMID- 31991090
OWN - NLM
STAT- MEDLINE
DCOM- 20201019
LR  - 20240124
IS  - 1535-4989 (Electronic)
IS  - 1044-1549 (Print)
IS  - 1044-1549 (Linking)
VI  - 62
IP  - 6
DP  - 2020 Jun
TI  - Applications and Approaches for Three-Dimensional Precision-Cut Lung Slices. 
      Disease Modeling and Drug Discovery.
PG  - 681-691
LID - 10.1165/rcmb.2019-0276TR [doi]
AB  - Chronic lung diseases (CLDs), such as chronic obstructive pulmonary disease, 
      interstitial lung disease, and lung cancer, are among the leading causes of 
      morbidity globally and impose major health and financial burdens on patients and 
      society. Effective treatments are scarce, and relevant human model systems to 
      effectively study CLD pathomechanisms and thus discover and validate potential 
      new targets and therapies are needed. Precision-cut lung slices (PCLS) from 
      healthy and diseased human tissue represent one promising tool that can closely 
      recapitulate the complexity of the lung's native environment, and recently, 
      improved methodologies and accessibility to human tissue have led to an increased 
      use of PCLS in CLD research. Here, we discuss approaches that use human PCLS to 
      advance our understanding of CLD development, as well as drug discovery and 
      validation for CLDs. PCLS enable investigators to study complex interactions 
      among different cell types and the extracellular matrix in the native 
      three-dimensional architecture of the lung. PCLS further allow for 
      high-resolution (live) imaging of cellular functions in several dimensions. 
      Importantly, PCLS can be derived from diseased lung tissue upon lung surgery or 
      transplantation, thus allowing the study of CLDs in living human tissue. 
      Moreover, CLDs can be modeled in PCLS derived from normal lung tissue to mimic 
      the onset and progression of CLDs, complementing studies in end-stage diseased 
      tissue. Altogether, PCLS are emerging as a remarkable tool to further bridge the 
      gap between target identification and translation into clinical studies, and thus 
      open novel avenues for future precision medicine approaches.
FAU - Alsafadi, Hani N
AU  - Alsafadi HN
AUID- ORCID: 0000-0002-1186-2517
AD  - Lung Bioengineering and Regeneration, Department of Experimental Medical Science.
AD  - Wallenberg Center for Molecular Medicine.
AD  - Lund Stem Cell Center, Faculty of Medicine, and.
AD  - Helmholtz Zentrum Munich, Lung Repair and Regeneration, Comprehensive Pneumology 
      Center, Member of the German Center for Lung Research, Munich, Germany.
FAU - Uhl, Franziska E
AU  - Uhl FE
AUID- ORCID: 0000-0002-0641-4162
AD  - Wallenberg Center for Molecular Medicine.
AD  - Vascular Biology, Department of Experimental Medical Science, Lund University, 
      Lund, Sweden.
FAU - Pineda, Ricardo H
AU  - Pineda RH
AD  - Division of Pulmonary Sciences and Critical Care Medicine, Department of 
      Medicine, University of Colorado Denver, Aurora, Colorado; and.
FAU - Bailey, Kolene E
AU  - Bailey KE
AD  - Division of Pulmonary Sciences and Critical Care Medicine, Department of 
      Medicine, University of Colorado Denver, Aurora, Colorado; and.
FAU - Rojas, Mauricio
AU  - Rojas M
AD  - Division of Respiratory, Allergy and Critical Care Medicine, The Dorothy P. and 
      Richard P. Simmons Center for Interstitial Lung Disease, University of 
      Pittsburgh, Pittsburgh, Pennsylvania.
FAU - Wagner, Darcy E
AU  - Wagner DE
AUID- ORCID: 0000-0003-3794-1309
AD  - Lung Bioengineering and Regeneration, Department of Experimental Medical Science.
AD  - Wallenberg Center for Molecular Medicine.
AD  - Lund Stem Cell Center, Faculty of Medicine, and.
AD  - Helmholtz Zentrum Munich, Lung Repair and Regeneration, Comprehensive Pneumology 
      Center, Member of the German Center for Lung Research, Munich, Germany.
FAU - Konigshoff, Melanie
AU  - Konigshoff M
AUID- ORCID: 0000-0001-9414-5128
AD  - Helmholtz Zentrum Munich, Lung Repair and Regeneration, Comprehensive Pneumology 
      Center, Member of the German Center for Lung Research, Munich, Germany.
AD  - Division of Pulmonary Sciences and Critical Care Medicine, Department of 
      Medicine, University of Colorado Denver, Aurora, Colorado; and.
LA  - eng
GR  - P50 AR060780/AR/NIAMS NIH HHS/United States
GR  - R01 HL123766/HL/NHLBI NIH HHS/United States
GR  - R01 HL141380/HL/NHLBI NIH HHS/United States
GR  - U01 HL145550/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Review
PL  - United States
TA  - Am J Respir Cell Mol Biol
JT  - American journal of respiratory cell and molecular biology
JID - 8917225
SB  - IM
MH  - Animals
MH  - Disease Models, Animal
MH  - Drug Discovery
MH  - Drug Evaluation, Preclinical
MH  - Humans
MH  - Idiopathic Pulmonary Fibrosis/pathology
MH  - Lung/*pathology
MH  - Lung Diseases/*pathology
MH  - Lung Neoplasms/pathology
MH  - Mice
MH  - Microtomy/*methods
MH  - Pulmonary Disease, Chronic Obstructive/pathology
MH  - Specimen Handling/*methods
PMC - PMC7401444
OTO - NOTNLM
OT  - PCLS
OT  - drug discovery
OT  - ex vivo lung disease
OT  - translation
EDAT- 2020/01/29 06:00
MHDA- 2020/10/21 06:00
PMCR- 2021/06/01
CRDT- 2020/01/29 06:00
PHST- 2020/01/29 06:00 [pubmed]
PHST- 2020/10/21 06:00 [medline]
PHST- 2020/01/29 06:00 [entrez]
PHST- 2021/06/01 00:00 [pmc-release]
AID - 10.1165/rcmb.2019-0276TR [doi]
PST - ppublish
SO  - Am J Respir Cell Mol Biol. 2020 Jun;62(6):681-691. doi: 10.1165/rcmb.2019-0276TR.