In a recent webinar titled “Developing Reproducible Small Animal Models to Better Reflect Lung Fibrosis Pathophysiology“, Dr. Elizabeth Redente shared insights for the study of idiopathic pulmonary fibrosis (IPF) and other interstitial lung diseases using murine models. Her focus centered on expanding the use and relevance of the single-dose bleomycin model to models of persistent fibrotic disease using genetics, age, sex and repetitive injury. Additionally, Dr. Redente discussed the occupational model of silicosis. Integrated into the model discussion are analytical methods to examine pathophysiology outcomes including pathology, lung physiology using flexiVent, microCT analysis and oxygen saturation. Lastly, Dr. Redente explored different methods of therapeutic intervention and targeted loss of fibroblast populations.
Key topics include:
Dr. Elizabeth Redente, PhD, ATSF, is an associate professor in the Division of Cell Biology in the Department of Pediatrics at National Jewish Health in Denver. Redente’s research focuses on the development of injury and repair of the lung, specifically how it relates to fibroblast cell phenotypes in pulmonary fibrosis. Redente’s research aims to develop a resolving process in fibrotic lungs by targeting pro-fibrotic fibroblasts to have a reduced pro-fibrotic phenotype and to undergo apoptosis followed by normal regeneration of the alveolar epithelium. Her focus is on understanding the role of Bcl-2 in non-resolving fibrosis animal models and in human fibrotic diseases with the goal of developing models of fibrosis that better recapitulate the histopathologic characteristics of human pulmonary fibrosis.
As a result of the fibrotic tissue accumulation, the lungs become stiffer. In humans, the disease is typically diagnosed using computed tomography (CT) scans and pulmonary function tests, both of which can be performed in small laboratory animals using the flexiVent. The ability of this integrated system to synchronize with micro-CT scanners, to provide static and dynamic measurements of respiratory mechanics, as well as to capture information on specific lung volumes or flows make it an extremely valuable tool to investigate pulmonary fibrosis at the preclinical level. As an example, changes in static compliance, acquired using the sensitive pressure-volume curves, allowed researchers to distinguish between degrees of disease severity or therapeutic efficacy. Furthermore, the flexiVent system’s Negative Pressure Forced Expiration (NPFE) extension offers additional insight by permitting outcomes similar to those commonly used in a clinical setting, such as the forced vital capacity (FVC).
Finally, the longitudinal aspect of the disease or the efficacy of a potential therapeutic approach over time can now be more easily assessed with the flexiVent since the recent publication of simple techniques of non-surgical subject integration to the system. Numerous examples of the use of the flexiVent in pulmonary fibrosis preclinical research can be found in the literature. Learn how a leading pulmonary fibrosis researcher uses the flexiVent in this interview.
SCIREQ recently collaborated with Regeneron to host a webinar that highlighted the role that preclinical lung function (FEV) can play in drug development, with an emphasis on dosing and efficacy.
Pulmonary Fibrosis (PF) is a type of interstitial lung disease with a poor prognosis and response to current therapies. During the progress of this disease, the build-up of fibrotic tissue leads to an overall rigidity of lung architecture, leading to a gradual decline in lung function.
Kumar et al. (2020) recently published a novel manuscript that combined work on cellular and mouse models shows that hyperglycemic conditions and the resultant metabolic alterations cause DNA
The flexiVent & Fibrosis
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