3D Ex Vivo Precision-Cut Lung Slice (PCLS) Model Introduction

Overview of Respiratory Infections

Respiratory diseases are one of the leading causes of death worldwide, imposing a significant health and economic burden on patients and healthcare systems. Therefore, there is an urgent need for technologies to optimize diagnostic and therapeutic strategies. The development of ex vivo human model systems, especially precision-cut lung slices (PCLS) model, contributes to the study of the pathogenesis of respiratory infections, leading to the discovery and validation of potential new targets and therapies.

Limitations of Traditional Models

Currently, research on the underlying disease mechanisms of respiratory diseases mainly relies on cell models and animal models. Although these traditional models provide crucial insights, each model has some limitations.

  • Cell culture models

Two-dimensional (2D) cell culture relies on immortalized cell lines with dramatically altered metabolic and gene expression profiles. More complex three-dimensional (3D) cell culture models recapitulate tissue architecture to some extent. However, these cellular models fail to recapitulate the true cellular richness and spatial complexity of the lung.

  • Animal models

Although animal models play a vital role in the study of respiratory diseases, experimental results produced by animals raised in well-controlled environments cannot reflect the conditions of human respiratory diseases. In addition, there are clear differences between animal model phenotypes and those observed in the clinic. Therefore, these models cannot be transferred between laboratory models and clinics.

Ex Vivo Precision-cut Lung Slices Models

A schematic diagram showing the procedure to generate PCLS.Fig 1. Procedure to generate PCLS.1

PCLS encompass all cell types in the tissue of interest and reflects disease-associated changes in the extracellular matrix. Biological experiment diagram-2. Distributed under CC BY 4.0, from Unsplash, without modification. PCLS preserve cellular complexity and lung architecture, providing a platform to study respiratory pathogens in a near-native setting. Biological experiment diagram-4. Distributed under CC BY 4.0, from Unsplash, without modification. The PCLS model system can effectively reduce the number of animals used for lung disease studies.
Biological experiment diagram-1. Distributed under CC BY 4.0, from Unsplash, without modification. PCLS play a crucial role in the paired analysis of multiple treatments in the same patient. Biological experiment diagram-3. Distributed under CC BY 4.0, from Unsplash, without modification. PCLS can be generated from different areas within the same lung to represent tissue and disease heterogeneity. Biological experiment diagram-5. Distributed under CC BY 4.0, from Unsplash, without modification.

Fig.2 Features of PCLS. (Creative Biolabs)

Applications

  • PCLS have the potential to support studies of key mechanisms of lung disease and early drug discovery.
  • Like other tissues, PCLS are amenable to classical endpoint analysis by histology and immunohistochemistry or metabolomics and proteomics.
  • PCLS are a vital strategy for exploring respiratory responses to specific stimuli, infections, and novel pharmaceutical compounds.

Maintenance of PCLS

Storing PCLS for future use by cryopreservation is a breakthrough in PCLS usage. Cryopreserved PCLS preserved important immune cell functions, including lymphocyte phagocytosis and proliferation. Thus, this storage modality allows for long-term storage of slices, enabling the collection of many phenotypes before experimentation.

PCLS are emerging as powerful tools for bridging the gap between target identification and translation into clinical research. Our diverse PCLS models open new avenues for future precision medicine approaches. If you are interested in our ex vivo PCLS models, please contact us in time for more details.

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Reference

  1. Liu, Guanghui et al. "Use of precision cut lung slices as a translational model for the study of lung biology." Respiratory research. 20,1 (2019): 162. Distributed under Open Access license CC BY 4.0, the original image's title was changed to "Procedure to generate PCLS".
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