Ex-vivo precision-cut lung slices (hPCLS) are perhaps the most complex non-animal model available to assess pulmonary injury. hPCLS are created from donor tissues obtained in a clinical setting and are created and maintained at IIVS using our custom hPCLS culture system. The tissue offers an advantage over other models since it contains all lung cell types present in the tissue at the time of slicing. Further, it retains the native architecture of the lung – including small airways and respiratory parenchyma. hPCLS have been maintained for many weeks and demonstrate changes not shown in other complex models of the lung. Acute (including robust cytokine responses, loss of viability, etc.) and chronic (including increases in activated macrophage staining, collagen deposition, tissue remodeling) toxicities can be monitored following test material-exposures. hPCLS have also been used to show no effect level and to identify drug concentration-specific reversibility of inflammatory marker expression – a key element in understanding whether an insult to respiratory tissue may persist or resolve after test material removal. As many diseases such as fibrosis or COPD are believed to be driven by chronic inflammatory processes, the availability of a long term pulmonary model of human origin that harbors vital immune cells and can deliver a wealth of data is a welcome addition to IIVS’s in vitro/ex vivo toolbox!
Recent advances at IIVS include a modified slicer and the development of a cryopreservation buffer for hPCLS. Our cryo-hPCLS can be stored frozen, retain viability for weeks after thaw, and allow repeat testing using the same donor.