Newswise —
Viola Vogel, a professor at ETH, and her senior assistant Mario C. Benn, are interested in understanding how the body grows and develops, including the processes behind embryo development, wound healing, and cancer spreading. They are particularly interested in the extracellular matrix (ECM), a fibrous structure surrounding body cells that is produced by the cells themselves and is a major component of all tissues. Unlike traditional biology research, which often focuses on studying cells and their metabolic processes in isolation from their natural environment, Vogel and Benn's work emphasizes the ECM and its interactions with cells.
Our body cells interact with a fibrous structure called the extracellular matrix. Scientists have found that these interactions are not only based on chemicals, but also on mechanics or physical forces. Cells can feel these physical forces from the extracellular matrix, like how we can feel touch or pressure.
Vogel and Benn, along with their research team, have successfully grown tissue in a lab and studied the process in detail. They discovered that the interactions between cells and the extracellular matrix are very important. Benn hopes to use these findings in the future to treat conditions such as wound-healing disorders, cancer, and connective-tissue diseases.
Cell transformation
The researchers studied two types of cells: fibroblasts and myofibroblasts. These cells are important for maintaining healthy tissue in the body. Fibroblasts help renew and maintain the extracellular matrix in our organs, while myofibroblasts are important for healing wounds and growing new tissue. Myofibroblasts produce large amounts of extracellular matrix and can also pull tissue together during wound healing.
Mario C. Benn, one of the researchers, explains that myofibroblasts are important for wound healing and tissue growth, but they need to change back to fibroblasts once their work is done. If they don't, the excessive formation of scar tissue, called fibrosis, can occur. Myofibroblasts are also present in cancer tissue, and high levels of these cells are associated with a poor prognosis for many cancers.
Three-dimensional matrix
Scientists Viola Vogel and Mario C. Benn wanted to understand how the extracellular matrix (ECM) influences the transformation of myofibroblasts into fibroblasts. They found that previous research had ignored the importance of the ECM. They developed a new method to study this process, as the conventional cell-culture methods led to the formation of an unnatural ECM. Studying cells without the ECM is like studying spiders without their web. Their method was originally developed at the Max Planck Institute of Colloids and Interfaces and was refined by the ETH scientists.
To study the role of the extracellular matrix (ECM) in tissue growth, Vogel and Benn use a silicone scaffold that has microscopic triangular-shaped clefts coated with specific proteins. This scaffold is placed in a tissue culture medium where new tissue forms in the clefts over a period of two weeks. As the tissue grows, it fills the clefts starting from the apex. This method allows for the formation of a more natural ECM compared to conventional cell-culture methods where cells grow flat across the culture dish.
During their research, Vogel and Benn observed that myofibroblasts are always present at the growth front of new tissue formation. They also discovered that myofibroblasts generate new extracellular matrix in this area, which starts out as provisional but later becomes more stable. Eventually, the myofibroblasts revert back to fibroblasts. Benn compared this process to the late phase of wound healing in subcutaneous human tissue.
The researchers discovered that one of the triggers for myofibroblasts to turn back into fibroblasts is the rapidly changing extracellular matrix. They found that a specific type of ECM fiber called fibronectin changing from a stretched to a relaxed state also promotes the reversion process. These findings suggest that similar interactions occur during wound healing.
The researchers intentionally disrupted the process of cell transformation by using different substances that alter the composition or structure of the extracellular matrix. This allowed them to mimic what happens in diseases such as fibrosis or cancer. In these conditions, instead of transforming into fibroblasts as they should, myofibroblasts are held in place by the extracellular matrix.
Future mechano-medicine
The researchers aim to use their mini tissue cultures to study the interaction between human cells and the extracellular matrix in more detail. This method will help to avoid animal testing in biomedical research and can also be used to test candidate substances during drug development. By understanding how myofibroblasts and fibroblasts transform into each other and controlling this process, they hope to make significant progress in conditions such as wound-healing disorders, fibrosis, and cancer.
Benn and Vogel also refer to a future field called mechano-medicine. This term describes the medical application of findings from the field of mechanobiology: the study of how cells can sense and process mechanical signals. In other words, mechano-medicine aims to apply the insights gained from mechanobiology to medical practice.
The researchers want to use mechano-medicine to create new ways to detect fibrotic tissue early. This is important because early detection is key to successfully treating conditions like pulmonary fibrosis. Current methods for screening cannot accurately detect myofibroblasts in lung tissue. By studying the extracellular matrix more closely, the researchers hope to find markers that make it easier to detect fibrosis and other similar diseases earlier.