Precision cut lung slices as an efficient tool for in vitro lung physio-pharmacotoxicology studies

Abstract

1.We review the specific approaches for lung tissue slices preparation and incubation systems and the research application fields in which lung slices proved to be a very efficient alternative to animal experimentation for biomechanical, physiological, pharmacological and toxicological approaches. 2.Focus is made on air-liquid interface dynamic organ culture systems that allow direct tissue exposure to complex aerosol and that best mimic in vivo lung tissue physiology. 3.A compilation of research applications in the fields of vascular and airway reactivity, mucociliary transport, polyamine transport, xenobiotic biotransformation, chemicals toxicology and complex aerosols supports the concept that precision cut lung slices are a very efficient tool maintaining highly differentiated functions similar to in vivo lung organ when kept under dynamic organ culture. They also have been successfully used for lung gene transfer efficiency assessment, for lung viral infection efficiency assessment, for studies of tissue preservation media and tissue post-conditioning to optimize lung tissue viability before grafting. 4.Taken all together, the reviewed studies point to a great interest for precision cut lung slices as an efficient and valuable alternative to in vivo lung organ experimentation.

Cryopreserved Human Precision-Cut Lung Slices as a Bioassay for Live Tissue Banking. A Viability Study of Bronchodilation with Bitter-Taste Receptor Agonists

“…The use of human precision-cut lung slices (hPCLSs) is becoming widely accepted as a research tool to investigate the physiological and pharmacological responses of normal and diseased lung tissue (1,2). PCLSs retain the organizational features of the in vivo lung, while providing microscopic access for individual cells (3)(4)(5)(6).…”

Murine precision-cut lung slices exhibit acute responses following exposure to gasoline direct injection engine emissions

“…Increased TNFα protein secretion relative to clean air controls (5% CO 2 , 20% O 2 , 75% N 2 ) was reported following PCLS exposure to particulate matter from diesel engine exhaust (Le Prieur et al, 2000;Morin et al, 2012).…”

Translational Research in Pharmacology and Toxicology Using Precision-Cut Tissue Slices

“…The preparation of liver and intestinal slices from human and rat tissue was recently described by de Graaf et al 17 and by Fisher et al 6 In order to keep the alveoli in the lung tissue open, lungs are usually lled with low-melting agarose via perfusion of the airways, aer which the solidied tissue is cored and sliced like liver. 18,19 The thickness of the slices can be adjusted rather precisely to the required thickness, being 200-250 mm for liver, 200-400 mm for intestine and 500 mm for lung. The thickness of the slices is limited by the diffusion of substrates and oxygen to the inner cell layers, which not only affects the viability of the inner cell layers 20 but also inuences the quantitative in vitro-in vivo extrapolation of metabolic rate.…”

“…Several comprehensive reviews were published recently and the reader is referred to these reviews and the references therein. 18,[38][39][40][41] PCTS were successfully applied to detect species-specic metabolism. A striking example is shown in De Kanter et al, 42 where the metabolism of testosterone is shown in human and rat liver, intestine, lung and kidney.…”