Small RNA-based formulations in precision cut lung slices - is there an alternative for in vivo/in vitro studies?

Precision cut lung slices (PCLS) are ex vivo models to study lung diseases. They have numerous advantages related to the presence of different cell types and extracellular matrix. They are an excellent platform to study the biological effects of delivering small molecules with therapeutic potential, such as non-coding RNAs. The aim of this review is to summarize the miRNA and siRNA research on the PCLS model to date and consider therapeutic potential of the proposed solutions.

The review focuses on the methodological aspects of delivery of RNA-based formulations, such as miRNA and siRNA, in the PCLSs model. It covers the area of RNA/miRNA isolation from PCLSs and methods of delivering miRNA and siRNA to PCLSs. Analysis of the reported solutions indicated the need for standardization, regarding the information on transfection efficacy at the RNA and protein levels is incomplete.

PCLSs are a promising model for studying small RNA-based drug delivery systems. However, existing models require consistent criteria and methods to assess the biological effect. Because of the heterogeneity of PCLS slices within the single studies, future experiments would benefit from including more independent replicates performed using different methods, in order to improve their reproducibility.