RT Journal Article
SR Electronic
T1 Watching the lung work: A cell culture based 3-D microfluidic device to challenge latest pulmonary drug delivery strategies with high end microscopy
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP P888
VO 44
IS Suppl 58
A1 Bonny Doshi
A1 Nina Hobi
A1 Maros Mastrak
A1 Thomas Haller
A1 Maja Gulic
A1 Manfred Frick
YR 2014
UL http://erj.ersjournals.com/content/44/Suppl_58/P888.abstract
AB During tissue development, lung cells are exposed to mechanical forces and communicate via biochemical signals directing their shape and function. The unique alveolar-capillary interface relates to cellular transport and cell differentiation and has particular impact on the understanding of pulmonary edema und cystic fibrosis. Our model allows to explore the delicate cellular compositions of lung tissue in the most physiological way:For that, we cultured freshly isolated AT II and immortal AT I cells from rat on the apical side in close contact to the air-liquid interface and HEMC-1 were seeded on the basolateral side. Our preliminary experiments were performed on cell culture inserts, thus we verified the functionality by measuring cell viability, morphogenesis, transepithelial resistance (TER) and tight junction protein expression under different conditions.The co-culture built a confluent monolayer and TER was significantly increased after two days interface contact. Applying different culture conditions had no effect on tight junction's expression and cell viability; though adding of dexamethason lead to a concentration dependent TER increase. Next, we will implement our coculture in a transparent microfluidic chamber that mimics the dynamic microenvironment of an intact lung and enables long-term cell culturing at the air-liquid-interface.Our 'artificial lung' model will facilitate the visualization of cellular processes in a live cell imaging manner. This approach could improve the current pathophysiological understanding of alveolar transport in general, and further accelerate pulmonary drug delivery research.