T cells are immune cells in our bodies that find and attack infected cells. Researchers are also engineering T cells to fight hard-to-target diseases like cancer. In adoptive cell therapies, T cells are trained against cancer markers. Successful therapies requires lots of T cells, which are multiplied many times outside of a person's body. However, currently this T cell expansion step takes several weeks. Figuring out how to grow T cells quickly in the lab is an important area of research.
One critical environmental variable is the stiffness of the cells’ underlying substrate, which is the surface on which they are grown. Previously, some reports claimed that cell growth increased with stiffness, while others argued that the cells grow optimally on softer substrates. In a new study published in the journal Biomaterials, researchers from Columbia University sought to more definitively understand how substrate stiffness impacts T cell activation and growth.
Their findings reconciled the long-standing scientific discrepancy. They discovered that T cells exhibited a two-phased response to changing substrate stiffness. Initially, both T cell proliferation, measured by the rate of cell division, and T cell activation increased with stiffness. But after a certain critical stiffness, these measures began to decrease. In other words, there is a "peak substrate stiffness" for growing T cells.
This work is primarily of importance to the design of future biomaterials for growing T cell populations for use in cancer-fighting adoptive cell therapies. Hopefully, these findings will make these therapies more accessible by reducing their timescale from weeks to days.