Application of Precision-Cut Lung Slices as an In Vitro Model for Research of Inflammatory Respiratory Diseases

Abstract

The leading cause of many respiratory diseases is an ongoing and progressive inflammatory response. Traditionally, inflammatory lung diseases were studied primarily through animal models, cell cultures, and organoids. These technologies have certain limitations, despite their great contributions to the study of respiratory diseases. Precision-cut lung slices (PCLS) are thin, uniform tissue slices made from human or animal lung tissue and are widely used extensively both nationally and internationally as an in vitro organotypic model. Human lung slices bridge the gap between in vivo and in vitro models, and they can replicate the living lung environment well while preserving the lungs’ basic structures, such as their primitive cells and trachea. However, there is no perfect model that can completely replace the structure of the human lung, and there is still a long way to go in the research of lung slice technology. This review details and analyzes the strengths and weaknesses of precision lung slices as an in vitro model for exploring respiratory diseases associated with inflammation, as well as recent advances in this field.

Perspectives on precision cut lung slices—powerful tools for investigation of mechanisms and therapeutic targets in lung diseases

“…Whether standardization of these various protocols for culture, treatment and measurement of outcomes is required to facilitate prolonged PCLS viability and reproducibility of outcomes is a subject of continued discussion among researchers in the field ( Patel et al, 2021 ; Liu et al, 2022 ; Preuß et al, 2022 ). Nevertheless, it is clear that significant insights can be gained using PCLS prepared from experimental animals and humans, extending beyond than cell-based studies.…”

Immunostimulatory Effect of Flagellin on MDR-Klebsiella-Infected Human Airway Epithelial Cells

“…PMNs play an important role in host defense against K. pneumoniae [ 34 ], by the release of high amounts of calprotectin and other antimicrobial proteins upon activation and the induction of neutrophil extracellular trap formation, aiding in limiting Klebsiella growth [ 20 , 21 , 35 , 36 ]. Future studies using organoids or advanced ex vivo models, such as precision-cut lung slices [ 37 ], supplemented with innate immune cells, could shed light on the interplay between the human lung epithelium and blood leukocytes in antibacterial defense against K. pneumoniae .…”

Lung regeneration: diverse cell types and the therapeutic potential

“…This method has some advantages over cell culture, but due to the limitation of the diffusion distance of nutrients in the culture medium, there is an upper limit to the thickness of the sections, which can only reflect part of the 3D structure of the lung. [200][201][202] The differences in respiratory system structures and development between mice and humans make the collection and analysis of human clinical lung tissue samples important. In particular, the development of single-cell transcriptome and spatial transcriptome also promotes the development of biological research from the hypothesis based on animal models of disease, with limited verification in human samples, to the hypothesis generation of unbiased molecular analysis based on human samples, and then verification using disease animal models.…”

“…This period can be extended to 21 days by changing the culture conditions. This method has some advantages over cell culture, but due to the limitation of the diffusion distance of nutrients in the culture medium, there is an upper limit to the thickness of the sections, which can only reflect part of the 3D structure of the lung 200–202 …”