Use of precision cut lung slices as a translational model for the study of lung biology

Abstract

Animal models remain invaluable for study of respiratory diseases, however, translation of data generated in genetically homogeneous animals housed in a clean and well-controlled environment does not necessarily provide insight to the human disease situation. In vitro human systems such as air liquid interface (ALI) cultures and organ-on-a-chip models have attempted to bridge the divide between animal models and human patients. However, although 3D in nature, these models struggle to recreate the architecture and complex cellularity of the airways and parenchyma, and therefore cannot mimic the complex cell-cell interactions in the lung. To address this issue, lung slices have emerged as a useful ex vivo tool for studying the respiratory responses to inflammatory stimuli, infection, and novel drug compounds. This review covers the practicality of precision cut lung slice (PCLS) generation and benefits of this ex vivo culture system in modeling human lung biology and disease pathogenesis.

Keywords: Precision cut lung slices; Respiratory biology; Translational model.

Fig. 1

A schematic diagram showing the procedure to generate PCLS. After infusing agarose into the lung, cylindrical cores of the lung can be prepared by using specific tissue coring tools, followed by cutting with tissue slicer, generating lung slices with uniform diameter and thickness

Fig. 2

Translational studies of asthma using mouse model and PCLS. Asthmatic patient experiences airway obstruction and hyperresponsiveness, bronchoconstriction as well as airway inflammation (eosinophilic and/or neutrophilic). Mouse model of allergic asthma induced by ovalbumin or house dust mite mimics relevant features of human allergic asthma upon allergic sensitization and challenge, resulting in allergen-specific response of airways. Asthmatic PCLS obtained from mouse and patients show significantly enhanced airway inflammation and hyperresponsiveness following stimulation of allergens and infections