Precision cut lung slices
[2] Precision cut lung slices are prepared using specialized equipment called Vibratomes, ensuring that the tissue remains viable and retains its structural and functional characteristics, making them ideal for a wide range of experimental applications.
[5] A critical advancement occurred in the 1940s when Stadie and Riggs introduced a microtome equipped with a thin razor blade, reducing thickness variability to about 5%.
[12] In practice, PCLS can maintain comparable viability and tissue homeostasis for 1 to 3 days, though extended periods can be achieved with optimized culture conditions.
[14] To address these limitations and enhance our understanding of asthma, researchers have turned to human Precision-cut Lung Slices (PCLS) obtained from both healthy and diseased individuals as a valuable ex vivo tool.
[15] PCLS derived from healthy and asthmatic lungs exhibit altered responses to various stimuli, including bronchoconstriction and hyperresponsiveness, which closely resemble those observed in patients and various animal models.
For instance, exposing guinea pigs or mice to cigarette smoke can reproduce key features of human COPD, including emphysema, small airway remodeling, and pulmonary hypertension.
For instance, PCLS obtained from smoke-exposed mice have shown elevated expression of chemokines when stimulated with viral mimics or influenza A virus.
Future studies employing PCLS from COPD patients hold the potential to enable both functional and phenotypic immune cell characterization, facilitating a more comprehensive understanding of molecular mechanisms underlying disease heterogeneity.
When exposed to TGF-β1 and cadmium chloride, both human and rat PCLS have displayed relevant pathohistological changes commonly observed in the early phases of lung fibrosis.
For example, caffeine, which inhibits TGF-β-induced increases in pro-fibrotic gene expression, has shown promise by significantly reducing fibrosis in PCLS from bleomycin-treated mice.
[24] The use of PCLS in IPF research holds great potential for understanding the disease's early stages, testing innovative therapies, and uncovering novel treatment strategies.
This system has shed light on which cells become infected within the intact lung, offering insights distinct from in vitro air-liquid interface cultures.
PCLS research in infection and inflammation enhances our understanding of immune responses, paving the way for insights into disease mechanisms and potential therapeutic strategies.
Precision-cut Lung Slices (PCLS) play a crucial role in evaluating novel therapeutic targets for asthma, especially as tolerance to conventional treatments like glucocorticoids and β2-receptor agonists becomes more common.
[35][36] However, it's important to note that specific cell types' distribution may vary among slices due to regional variability within the lung, especially in the presence of non-uniform disease-related changes.
[39] PCLS have found applications in a wide range of respiratory research areas, including asthma, COPD, idiopathic pulmonary fibrosis, allergies, infections, and toxicology studies.
Firstly, PCLS represent a static "snapshot" of lung tissue at the time of excision, lacking access to the dynamic, recruitable immune system present in living organisms.
When studying diseases, such as respiratory conditions, this heterogeneity can complicate data interpretation, requiring careful statistical analysis to account for variability between slices.
