TY - JOUR
T1 - Pressure induced lung injury in a novel in vitro model of the alveolar interface
T2 - Protective effect of dexamethasone
AU - Nalayanda, Divya D.
AU - Fulton, William B.
AU - Colombani, Paul M.
AU - Wang, Tza Huei
AU - Abdullah, Fizan
PY - 2014/1
Y1 - 2014/1
N2 - Purpose The lungs of infants born with congenital diaphragmatic hernia suffer from immaturity as well as the short and long term consequences of ventilator-induced lung injury, including chronic lung disease. Antenatal and postnatal steroids are among current strategies promoted to treat premature lungs and limit long term morbidity. Although studied in whole-animal models, insight into ventilator-induced injury at the alveolar-capillary interface as well as the benefits of steroids, remains limited. The present study utilizes a multi-fluidic in vitro model of the alveolar-interface to analyze membrane disruption from compressive aerodynamic forces in dexamethasone-treated cultures. Methods Human alveolar epithelial cell lines, H441 and A549, were cultured in a custom-built chamber under constant aerodynamic shear followed by introduction of pressure stimuli with and without dexamethasone (0.1μM). On-chip bioelectrical measurements were noted to track changes to the cellular surface and live-dead assay to ascertain cellular viability. Results Pressure-exposed alveolar cultures demonstrated a significant drop in TEER that was less prominent with an underlying extracellular-matrix coating. Addition of dexamethasone resulted in increased alveolar layer integrity demonstrated by higher TEER values. Furthermore, dexamethasone-treated cells exhibited faster recovery, and the effects of pressure appeared to be mitigated in both cell types. Conclusion Using a novel in vitro model of the alveolus, we demonstrate a dose-response relationship between pressure application and loss of alveolar layer integrity. This effect appears to be alleviated by dexamethasone and matrix sub-coating.
AB - Purpose The lungs of infants born with congenital diaphragmatic hernia suffer from immaturity as well as the short and long term consequences of ventilator-induced lung injury, including chronic lung disease. Antenatal and postnatal steroids are among current strategies promoted to treat premature lungs and limit long term morbidity. Although studied in whole-animal models, insight into ventilator-induced injury at the alveolar-capillary interface as well as the benefits of steroids, remains limited. The present study utilizes a multi-fluidic in vitro model of the alveolar-interface to analyze membrane disruption from compressive aerodynamic forces in dexamethasone-treated cultures. Methods Human alveolar epithelial cell lines, H441 and A549, were cultured in a custom-built chamber under constant aerodynamic shear followed by introduction of pressure stimuli with and without dexamethasone (0.1μM). On-chip bioelectrical measurements were noted to track changes to the cellular surface and live-dead assay to ascertain cellular viability. Results Pressure-exposed alveolar cultures demonstrated a significant drop in TEER that was less prominent with an underlying extracellular-matrix coating. Addition of dexamethasone resulted in increased alveolar layer integrity demonstrated by higher TEER values. Furthermore, dexamethasone-treated cells exhibited faster recovery, and the effects of pressure appeared to be mitigated in both cell types. Conclusion Using a novel in vitro model of the alveolus, we demonstrate a dose-response relationship between pressure application and loss of alveolar layer integrity. This effect appears to be alleviated by dexamethasone and matrix sub-coating.
KW - Air-interface culture
KW - Alveolar cells
KW - Dexamethasone
KW - Pressure-induced injury
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U2 - 10.1016/j.jpedsurg.2013.09.030
DO - 10.1016/j.jpedsurg.2013.09.030
M3 - Article
C2 - 24439582
AN - SCOPUS:84892615905
SN - 0022-3468
VL - 49
SP - 61
EP - 65
JO - Journal of Pediatric Surgery
JF - Journal of Pediatric Surgery
IS - 1
ER -