Flagship has substantial experience in measuring fibrosis in tissue biopsies, across a wide number of disease areas. Fibrosis can be defined as the formation of excess fibrous connective tissue in an organ or tissue. When fibrois derives from a single cell line it is called a fibroma, and when it forms in response to injure can be called scarring. By depositing connective tissue, it can interfere with the architecture and normal function of the organ or tissue. Both the state of excess fibrous tissue as well as the healing process of connective tissue deposition is often called fibrosis.
Flagship is developing a number of techniques, from tissue acquistion through histology to quantitative image analysis, to better measure fibrosis in tissue biopsies. Two examples describe some of Flagship’s experience in this area.
Liver Fibrosis in NASH (Nonalcoholic steatohepatitus)
In liver fibrosis, Nonalcoholic steatohepatitis or NASH is a common, often “silent” chronic liver disease. While resembling alcoholic liver disease, it occurs in people who drink little or no alcohol. The lesions most commonly accepted for NASH include steatosis, hepatocyte ballooning degeneration, mild diffuse lobular mixed acute and chronic inflammation, and perivenular, perisinusoidal collagen deposition. Progression of fibrosis may result in bridging septa and cirrhosis, ultimately leading to liver failure. There are no specific therapies for NASH. Current treatment focuses on controlling associated medical conditions, such as diabetes and obesity, and on monitoring for progression. Emerging antifibrotic therapies are aimed at inhibiting the accumulation of fibrogenic cells and/or preventing the deposition of extracellular matrix proteins. Development of a reproducible murine model recapitulating the progressive nature of NASH with accurate and reproducible detection and analysis of fibrosis progression would be a useful tool for studying the natural history, molecular mechanisms and biology of NASH.
Read more about evaluating NASH fibrosis on Flagship’s blog.
Measuring Cardiac Fibrosis
Cardiac fibrosis refers both to the proliferation of fibroblasts in cardiac smooth muscle as well as an abnormal thickening of heart values, related to the proliferation of fibroblasts. Heart failure can result due to the thickening and poorer performing cardiac muscle tissue. Under normal conditions, fibrocyte cells secrete collagen, but when over-activated, the result is thickening and valve fibrosis, on the tricuspid valve and also the pulmonary value.
More fibrosis examples: