An aggregate of stem cells taken from the mouse embryo in early stages of development. Image credit: Witteveldt et al. (CC BY 4.0)
Living cells are under constant attack from disease-causing agents, such as viruses and bacteria. As a result, they have evolved various protective mechanisms to fight off these agents. One of the most important ways that an animal cell protects itself from infection is through the interferon response, which warns the cell of approaching viruses, prompting it to prepare to defend itself. Virtually all healthy cells have an active interferon response, except for stem cells, which have switched off this defensive mechanism, for unknown reasons. This makes stem cells more susceptible to infections.
Stem cells are specialized cells that play an essential role in developing the early embryo. The two defining characteristics of these cells – their ability to divide indefinitely, and develop into all cell types – offers great therapeutic potential, as they can be used to ‘replace’ damaged cells and tissues. However, without an interferon response, stem cells are likely to become infected when moved into a new environment, counteracting their therapeutic benefits. Now, Witteveldt et al. investigate how stem cells turn off this viral defence mechanism, and whether turning it back on will affect their ability to divide and form new tissues.
Using stem cells taken from the embryos of mice, Witteveldt et al. found that the interferon response is turned off by specific small molecules of RNA. These small RNA molecules block a protein in the pathway that recognizes viruses and activates a defence. Genetically engineering stem cells to be deficient in these small RNA molecules led to an increased resistance to viral infections. Importantly, modifying stem cells in this manner had no obvious impact on the characteristic traits that give stem cells their therapeutic potential.
Temporarily increasing the interferon response of stem cells as they are moved into a new environment could potentially make stem cell treatments more effective. However, more work is needed to investigate whether the same approach can be applied to human cells, and determine what negative effects may be associated with turning on the interferon response.
