PMID- 36263353
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221021
IS  - 2296-4185 (Print)
IS  - 2296-4185 (Electronic)
IS  - 2296-4185 (Linking)
VI  - 10
DP  - 2022
TI  - A tunable physiomimetic stretch system evaluated with precision cut lung slices 
      and recellularized human lung scaffolds.
PG  - 995460
LID - 10.3389/fbioe.2022.995460 [doi]
LID - 995460
AB  - Breathing exposes lung cells to continual mechanical stimuli, which is part of 
      the microenvironmental signals directing cellular functions together with the 
      extracellular matrix (ECM). Therefore, developing systems that incorporate both 
      stimuli is urgent to fully understand cell behavior. This study aims to introduce 
      a novel in vitro culture methodology combining a cyclic stretch that simulates in 
      vivo breathing with 3D cell culture platforms in the form of decellularized lung 
      slices (DLS) and precision cut lung slices (PCLS). To this end, we have 
      constructed a device that mimics the amplitudes and frequencies of distensions 
      seen in the breathing human lung. For its validation, we cultured H441 lung 
      epithelial cells in human DLS exposed to 16 stretch cycles per minute with a 10% 
      stretch amplitude. Cell viability (resazurin reduction), proliferation (Ki-67) 
      and YAP1 activation were evaluated at 24 and 96 h by immunohistochemistry, while 
      the expression of SFTPB, COL3A1, COL4A3 and LAMA5 was evaluated by qPCR. Cyclic 
      stretch induced an increase in SFTPB expression after 24 h without a concomitant 
      increase in the stretch responsive gene YAP1. Moreover, the ECM milieu lowered 
      the expression of the basement membrane protein genes COL4A3 and LAMA5 compared 
      to tissue culture plastic control cultures, but no effect was observed by the 
      mechanical stimuli. The device also confirmed good compatibility with PCLS 
      culture, showing preserved morphology and metabolism in rat PCLS after 72 h of 
      mechanical stretch. Thus, we present a novel device and methodology for the easy 
      assembling and study of lung tissue slice cultures subjected to physiomimetic 
      mechanical stimuli, which shows promise for future studies of cell and tissue 
      function in a lung ECM milieu with physiological or pathological mechanical 
      stimuli.
CI  - Copyright (c) 2022 Rosmark, Ibanez-Fonseca, Thorsson, Dellgren, Hallgren, Larsson 
      Callerfelt, Elowsson and Westergren-Thorsson.
FAU - Rosmark, Oskar
AU  - Rosmark O
AD  - Lung Biology, Department of Experimental Medical Science, Lund University, Lund, 
      Sweden.
FAU - Ibanez-Fonseca, Arturo
AU  - Ibanez-Fonseca A
AD  - Lung Biology, Department of Experimental Medical Science, Lund University, Lund, 
      Sweden.
FAU - Thorsson, Johan
AU  - Thorsson J
AD  - Lung Biology, Department of Experimental Medical Science, Lund University, Lund, 
      Sweden.
FAU - Dellgren, Goran
AU  - Dellgren G
AD  - Transplant Institute and Department of Cardiothoracic Surgery, Sahlgrenska 
      University Hospital, Gothenburg, Sweden.
FAU - Hallgren, Oskar
AU  - Hallgren O
AD  - Division of Thoracic Surgery, Department of Clinical Sciences, Lund University, 
      Lund, Sweden.
FAU - Larsson Callerfelt, Anna-Karin
AU  - Larsson Callerfelt AK
AD  - Lung Biology, Department of Experimental Medical Science, Lund University, Lund, 
      Sweden.
FAU - Elowsson, Linda
AU  - Elowsson L
AD  - Lung Biology, Department of Experimental Medical Science, Lund University, Lund, 
      Sweden.
FAU - Westergren-Thorsson, Gunilla
AU  - Westergren-Thorsson G
AD  - Lung Biology, Department of Experimental Medical Science, Lund University, Lund, 
      Sweden.
LA  - eng
PT  - Journal Article
DEP - 20221003
PL  - Switzerland
TA  - Front Bioeng Biotechnol
JT  - Frontiers in bioengineering and biotechnology
JID - 101632513
PMC - PMC9574011
OTO - NOTNLM
OT  - 3D
OT  - epithelial cells
OT  - extracellular matrix
OT  - lung
OT  - mechanical stimuli
OT  - precision cut lung slice
OT  - stretch
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/10/21 06:00
MHDA- 2022/10/21 06:01
PMCR- 2022/01/01
CRDT- 2022/10/20 03:03
PHST- 2022/07/15 00:00 [received]
PHST- 2022/09/13 00:00 [accepted]
PHST- 2022/10/20 03:03 [entrez]
PHST- 2022/10/21 06:00 [pubmed]
PHST- 2022/10/21 06:01 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 995460 [pii]
AID - 10.3389/fbioe.2022.995460 [doi]
PST - epublish
SO  - Front Bioeng Biotechnol. 2022 Oct 3;10:995460. doi: 10.3389/fbioe.2022.995460. 
      eCollection 2022.