Newcells has developed an in vitro Fibroblast-to-Myofibroblast Transition (FMT) assay as a valuable tool for studying fibrotic diseases and developing new therapeutics in drug discovery
Fibrotic diseases, including liver fibrosis, pulmonary fibrosis, and renal fibrosis, are characterized by the excessive deposition of extracellular matrix (ECM) components, leading to the formation of fibrous tissue that replaces functional tissue and impairs organ function. Myofibroblasts, a subpopulation of fibroblasts with contractile properties, play a critical role in tissue fibrosis by producing and depositing ECM proteins. The specific targeting of myofibroblasts has long presented a scientific and clinical challenge, in part due to the lack of reliable and predictive in vitro fibrosis models that can recapitulate the complexity and pathophysiology of fibrosis. The use of disease relevant in vitro assays allows the assessment of efficacy and safety profiles of therapeutic candidates.
The transition to myofibroblasts is a critical step in the development of fibrotic diseases and is regulated by various cytokines and growth factors, as well as mechanical stress. Our FMT assay uses physiological signals and cues to mimic fibrosis to aid the development of new anti-fibrotic therapeutics. Our FMT-assay can also be utilised to determine the fibrotic potential of drug candidates. We are able to measure changes in the expression levels of α-smooth muscle actin (αSMA), a well-known myofibroblast marker and hallmark of fibrotic disease. Our assay also allows quantification of the disease relevant ECM proteins collagen I and collagen III.
By exposing fibroblasts to physiologically relevant concentrations of transforming growth factor – β (TGF-β1) we can assess the ability of potential therapeutics to reduce FMT and determine their effects on collagen synthesis and deposition. Our high-throughput (384-well format) allows rapid screening and evaluation of potential anti-fibrotic compounds and their effects on ECM expression. In addition to the regulation of collagen synthesis and αSMA expression our FMT assay can be used to study cellular proliferation in response to TGF-β1 and therapeutic molecules.
Our FMT assay has several advantages for the study of fibrotic disease, which make our FMT assay an attractive option for early-drug discovery:
- High-throughput format using a disease relevant stimulus and primary human fibroblasts from multiple donors to capture donor-to-donor variation.
- Our high-content imaging platform allows the simultaneous measurement of multiple fibrotic proteins to allow rapid data generation.
- Internal assay controls ensure consistency across plates to facilitate the evaluation of a large number of therapeutic candidates.
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Dr Amy Mawdesley
27th February, 2023