Altering Extracellular Matrix Triggers Cell Transition

ETH Professor Viola Vogel and her senior assistant Mario C. Benn have been investigating the details behind how body tissue grows. Their study shows the importance of the interactions between cells and the extracellular matrix (ECM), which are not exclusively biochemical but mechanical or physical. Alongside a team of researchers, Vogel and Benn have been able to replicate tissue growth in vitro and study this process in detail.

The group primarily focused on two cell types: fibroblasts and myofibroblasts. Fibroblasts are found in the connective tissue of organs and ensure the extracellular matrix remains healthy, while myofibroblasts play a crucial role in wound healing and new tissue growth.

Myofibroblasts produce large amounts of ECM during wound healing and are strong enough to pull together tissue. Once their work is done, it is crucial that these myofibroblasts transform back into the less active fibroblasts — otherwise, it can lead to fibrosis.

High levels of myofibroblasts are associated with a poor prognosis in many cancers. The researchers used a silicone scaffold coated with specific proteins with microscopic triangular clefts to replicate tissue growth in vitro. They observed how myofibroblasts form new ECM in the area of tissue that is being newly formed before converting back into fibroblasts.

The researchers found that rapidly changing ECM is one of the triggers to reverse myofibroblasts to fibroblasts. Moreover, this reversion is promoted when a certain type of ECM fiber, fibronectin, changes from a stretched to a relaxed state. The team believes that similar interactive processes occur during wound healing. By interfering with the cell transition, they were able to replicate what occurs with pathologies such as fibrosis or cancer, where myofibroblasts are stabilized by the extracellular matrix instead of reverting to fibroblasts, as in healthy tissue.

Vogel and Benn believe that miniature tissue cultures will help them decipher further details of the interaction between human cells and their extracellular matrix. This will not only avoid animal testing but could also be used to test candidate substances during drug development.

By understanding how myofibroblasts and fibroblasts change into one another and controlling that process, they hope to make further progress with wound-healing disorders, cancer, and connective-tissue diseases. These findings, published in Science Advances, underline the importance of cellular interactions and extracellular matrix and could lead to new therapies in the future.