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Human,Lungs,Anatomy,Scientific,Background.,3d,Illustration

Precision Cut Lung Slices: Unraveling the Intricacies of Asthma Research

Asthma, a chronic respiratory disease affecting millions worldwide, remains a significant health concern. In the quest for better treatment options, precision cut lung slices (PCLS) have emerged as a cutting-edge tool in preclinical asthma research. These ex vivo lung tissue samples offer researchers invaluable insights into the complex mechanisms of asthma pathogenesis, enabling the development of more targeted and effective therapies. In this blog, we explore the importance of using PCLS for enhancing our understanding of this multifaceted condition.

Capturing Dynamic Airway Constriction

A defining feature of asthma is the hyperreactivity of airways, leading to bronchoconstriction and breathing difficulties. With PCLS, researchers can observe and measure dynamic airway constriction in real-time using the physioLens. This capacity to mimic bronchoconstriction under controlled conditions facilitates the investigation of different triggers and the evaluation of potential bronchodilators and anti-inflammatory compounds. The unique advantage of PCLS is its ability to capture the heterogeneity of airway hyperresponsiveness, a complex phenomenon inherently tied to observable airway dynamics. The dose-response relationship detectable within PCLS permits researchers to disentangle the intricacies of agonist sensitivity from the heightened maximum contractility. Furthermore, the integration of airway contractility with dimensions, spatial orientation, and other morphological attributes opens avenues for a deeper comprehension of the underlying mechanisms.

Preserving Tissue Architecture

One of the most significant advantages of employing PCLS in asthma research is the preservation of the lung tissue’s native architecture. Obtained through specialized techniques that maintain the delicate structure of the lungs, PCLS closely mimic in vivo conditions, providing a more relevant and translational representation of the disease than traditional cell cultures. This aspect allows researchers to study cellular interactions, tissue responses, and the effects of potential treatments in a controlled yet physiologically relevant environment.

Exploring Inflammatory Responses

Chronic inflammation of the airways is a hallmark of asthma. PCLS offer a unique window into the inflammatory processes within the lung tissue. Researchers can simulate the introduction of allergens or irritants to these slices, mimicking asthma exacerbations and measuring the subsequent inflammatory responses. This knowledge is instrumental in uncovering the specific cellular and molecular mechanisms involved in asthma’s inflammatory pathways, enabling the identification of promising targets for anti-inflammatory drugs.

Personalized Medicine and Drug Screening

Each asthma patient presents a unique set of characteristics and triggers, making personalized treatment strategies highly beneficial. PCLS contribute to the development of personalized medicine by allowing researchers to analyze individual patient samples in a controlled setting. These slices serve as a platform for drug screening, helping to identify the most effective treatment options for particular asthma phenotypes and patient subgroups, thus paving the way for more tailored therapeutic approaches.

Reducing Animal Testing

Ethical concerns surrounding animal testing have prompted the scientific community to seek alternative research methods. PCLS, derived from human or animal lung tissues, provide a viable and more ethically sound option. By using PCLS, researchers can significantly reduce the number of animal experiments while still obtaining clinically relevant data. This approach aligns with the principles of the 3Rs (Replacement, Reduction, and Refinement) and advances the field of asthma research in a more responsible and compassionate manner.

Conclusion

Precision cut lung slices (PCLS) have revolutionized preclinical asthma research, offering researchers an intricate and physiologically relevant platform to explore the complexities of this widespread respiratory disease. From preserving tissue architecture to enabling personalized medicine and reducing the reliance on animal testing, PCLS play a pivotal role in advancing our understanding of asthma pathogenesis and the development of targeted therapies. With ongoing advancements in technology and research methodologies, the integration of PCLS in asthma studies holds the promise of brighter prospects for patients worldwide, leading to improved management and, ultimately, a better quality of life for those living with asthma.

We are proud to introduce the physioLens at ATS this year; a scientific platform that provides accurate physiological and image-based outcomes in a reproducible fashion. It includes an automated microscope and fluid handling system.

The physioLens is capable of capturing images anywhere on slices in a 6 well plate and apply doses without user intervention. Images are analyzed in real-time to provide bronchoconstriction data. 

Dosing

Agonists are provided to the slice without user intervention by a dosing nozzle, that can provide a 95% media exchange in less than 20 seconds. In addition, eight dosing bottles are provided to complete a detailed dose response automatically. 

Image analysis: Images of airways are automatically processed to capture the lumen contours and then calculate bronchoconstriction. 

Slice scanning

Navigating a slice is not necessary with our airway configuration wizard complete with full slice mapping. Fine tune the positions of interest with our click-and-drag XY navigation. 

Tissue slices are held in place with a transparent when wet membrane allowing seamless sample-mounting.

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