PMID- 37953708
OWN - NLM
STAT- MEDLINE
DCOM- 20240207
LR  - 20240218
IS  - 2192-2659 (Electronic)
IS  - 2192-2640 (Print)
IS  - 2192-2640 (Linking)
VI  - 13
IP  - 4
DP  - 2024 Feb
TI  - Hydrogel-Embedded Precision-Cut Lung Slices Model Lung Cancer Premalignancy Ex 
      Vivo.
PG  - e2302246
LID - 10.1002/adhm.202302246 [doi]
AB  - Lung cancer is the leading global cause of cancer-related deaths. Although 
      smoking cessation is the best prevention, 50% of lung cancer diagnoses occur in 
      people who have quit smoking. Research into treatment options for high-risk 
      patients is constrained to rodent models, which are time-consuming, expensive, 
      and require large cohorts. Embedding precision-cut lung slices (PCLS) within an 
      engineered hydrogel and exposing this tissue to vinyl carbamate, a carcinogen 
      from cigarette smoke, creates an in vitro model of lung cancer premalignancy. 
      Hydrogel formulations are selected to promote early lung cancer cellular 
      phenotypes and extend PCLS viability to six weeks. Hydrogel-embedded PCLS are 
      exposed to vinyl carbamate, which induces adenocarcinoma in mice. Analysis of 
      proliferation, gene expression, histology, tissue stiffness, and cellular content 
      after six weeks reveals that vinyl carbamate induces premalignant lesions with a 
      mixed adenoma/squamous phenotype. Putative chemoprevention agents diffuse through 
      the hydrogel and induce tissue-level changes. The design parameters selected 
      using murine tissue are validated with hydrogel-embedded human PCLS and results 
      show increased proliferation and premalignant lesion gene expression patterns. 
      This tissue-engineered model of human lung cancer premalignancy is the foundation 
      for more sophisticated ex vivo models that enable the study of carcinogenesis and 
      chemoprevention strategies.
CI  - (c) 2023 Wiley-VCH GmbH.
FAU - Blomberg, Rachel
AU  - Blomberg R
AUID- ORCID: 0000-0002-1776-0044
AD  - Department of Bioengineering, University of Colorado, Denver |Anschutz, Aurora, 
      CO, 80045, USA.
FAU - Sompel, Kayla
AU  - Sompel K
AD  - Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine 
      University of Colorado, Anschutz Medical Campus, Aurora, CO, 80045, USA.
FAU - Hauer, Caroline
AU  - Hauer C
AD  - Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine 
      University of Colorado, Anschutz Medical Campus, Aurora, CO, 80045, USA.
FAU - Smith, Alex J
AU  - Smith AJ
AD  - Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine 
      University of Colorado, Anschutz Medical Campus, Aurora, CO, 80045, USA.
FAU - Pena, Brisa
AU  - Pena B
AD  - Department of Bioengineering, University of Colorado, Denver |Anschutz, Aurora, 
      CO, 80045, USA.
AD  - Cardiovascular Institute & Adult Medical Genetics, University of Colorado, 
      Anschutz Medical Campus, Aurora, CO, 80045, USA.
FAU - Driscoll, Jennifer
AU  - Driscoll J
AD  - Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, 
      National Jewish Health, Denver, CO, 80206, USA.
FAU - Hume, Patrick S
AU  - Hume PS
AD  - Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine 
      University of Colorado, Anschutz Medical Campus, Aurora, CO, 80045, USA.
AD  - Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, 
      National Jewish Health, Denver, CO, 80206, USA.
FAU - Merrick, Daniel T
AU  - Merrick DT
AD  - Department of Pathology, University of Colorado, Anschutz Medical Campus, Aurora, 
      CO, 80045, USA.
FAU - Tennis, Meredith A
AU  - Tennis MA
AD  - Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine 
      University of Colorado, Anschutz Medical Campus, Aurora, CO, 80045, USA.
FAU - Magin, Chelsea M
AU  - Magin CM
AUID- ORCID: 0000-0002-6988-8584
AD  - Department of Bioengineering, University of Colorado, Denver |Anschutz, Aurora, 
      CO, 80045, USA.
AD  - Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine 
      University of Colorado, Anschutz Medical Campus, Aurora, CO, 80045, USA.
AD  - Department of Pediatrics, University of Colorado, Anschutz Medical Campus, 
      Aurora, CO, 80045, USA.
LA  - eng
GR  - R21 CA252172/CA/NCI NIH HHS/United States
GR  - T32HL007085/HL/NHLBI NIH HHS/United States
GR  - K25 HL148386/HL/NHLBI NIH HHS/United States
GR  - K08 HL155894/HL/NHLBI NIH HHS/United States
GR  - K25HL148386/GF/NIH HHS/United States
GR  - T32 HL007085/HL/NHLBI NIH HHS/United States
PT  - Journal Article
DEP - 20231127
PL  - Germany
TA  - Adv Healthc Mater
JT  - Advanced healthcare materials
JID - 101581613
RN  - 0 (Hydrogels)
RN  - 7Y2431GOM5 (vinyl carbamate)
RN  - 3IN71E75Z5 (Urethane)
SB  - IM
MH  - Humans
MH  - Mice
MH  - Animals
MH  - Hydrogels
MH  - *Lung Neoplasms/pathology
MH  - Lung/pathology
MH  - Urethane
MH  - *Precancerous Conditions
PMC - PMC10872976
MID - NIHMS1950299
OTO - NOTNLM
OT  - biomaterials
OT  - hydrogels
OT  - in vitro models
OT  - lung cancer
OT  - precision-cut lung slices
OT  - premalignancy
OT  - tissue engineering
EDAT- 2023/11/13 06:43
MHDA- 2024/02/07 06:43
PMCR- 2025/02/01
CRDT- 2023/11/13 03:48
PHST- 2023/10/17 00:00 [revised]
PHST- 2023/07/14 00:00 [received]
PHST- 2025/02/01 00:00 [pmc-release]
PHST- 2024/02/07 06:43 [medline]
PHST- 2023/11/13 06:43 [pubmed]
PHST- 2023/11/13 03:48 [entrez]
AID - 10.1002/adhm.202302246 [doi]
PST - ppublish
SO  - Adv Healthc Mater. 2024 Feb;13(4):e2302246. doi: 10.1002/adhm.202302246. Epub 
      2023 Nov 27.