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Applications and Approaches for Three-Dimensional Precision-Cut Lung Slices. Disease Modeling and Drug Discovery

Alsafadi, Hani N LU orcid ; Uhl, Franziska E. LU ; Pineda, Ricardo H. ; Bailey, Kolene E. ; Rojas, Mauricio ; Wagner, Darcy E LU orcid and Königshoff, Melanie (2020) In American Journal of Respiratory Cell and Molecular Biology 62(6). p.681-691
Abstract

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... (More)

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.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
drug discovery, ex vivo lung disease, PCLS, translation
in
American Journal of Respiratory Cell and Molecular Biology
volume
62
issue
6
pages
681 - 691
publisher
American Thoracic Society
external identifiers
  • pmid:31991090
  • scopus:85084077561
ISSN
1044-1549
DOI
10.1165/rcmb.2019-0276TR
language
English
LU publication?
yes
id
8c023ea6-8b01-46b3-8f7f-2474c606252c
date added to LUP
2020-01-29 15:58:10
date last changed
2022-04-18 20:10:30
@article{8c023ea6-8b01-46b3-8f7f-2474c606252c,
  abstract     = {{<p>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.</p>}},
  author       = {{Alsafadi, Hani N and Uhl, Franziska E. and Pineda, Ricardo H. and Bailey, Kolene E. and Rojas, Mauricio and Wagner, Darcy E and Königshoff, Melanie}},
  issn         = {{1044-1549}},
  keywords     = {{drug discovery; ex vivo lung disease; PCLS; translation}},
  language     = {{eng}},
  month        = {{06}},
  number       = {{6}},
  pages        = {{681--691}},
  publisher    = {{American Thoracic Society}},
  series       = {{American Journal of Respiratory Cell and Molecular Biology}},
  title        = {{Applications and Approaches for Three-Dimensional Precision-Cut Lung Slices. Disease Modeling and Drug Discovery}},
  url          = {{http://dx.doi.org/10.1165/rcmb.2019-0276TR}},
  doi          = {{10.1165/rcmb.2019-0276TR}},
  volume       = {{62}},
  year         = {{2020}},
}