Lab-on-chip recreates damaged heart
A small device replicates the conditions seen early on in damaged heart tissue to better understand how it can be repaired.
When the supply of oxygen to the heart is reduced, its cells start to die within hours, the heart muscle becomes less able to contract, and the area becomes inflamed. This inflammation is accompanied by an influx of immune cells. It also activates other cells known as cardiac fibroblasts that help to break down the framework of molecules that supported the damaged heart tissue and replace it with a scar. This response is part of the normal repair process, but it can lead to the formation of scar tissue in non-damaged areas of the heart. Excess scar tissue makes the heart muscle less able to contract and increases the affected individual’s chance of dying.
Understanding how this repair process works is an important step in developing strategies to minimise the damage caused by coronary artery disease or heart attacks. However, existing laboratory models are only partly able to recreate the conditions seen in real heart tissue. To properly understand the response at the level of living cells, a more complete model is needed.
Giovanni Ugolini and co-workers now report improvements to a small device, referred to as a lab-on-chip, that can subject cells to mechanical strain. The improvements mean the device could also recreate other conditions seen early on in damaged heart tissue, specifically the reduced supply of oxygen. Replicating combinations of mechanical changes and oxygen supplies meant that the impact of these conditions on human cardiac fibroblasts could be directly observed in the laboratory for the first time. Ugolini and co-workers found that a lack of contraction and low oxygen levels triggered the cardiac fibroblasts to produce inflammatory molecules and molecules associated with the formation of scar tissue. This resembles the response seen in living hearts.
The next step is to improve the lab-on-chip device further by adding other cell types, including heart muscle cells and immune cells. A more complete model may aid future research into how our hearts operate in both health and disease.
To find out more
Read the eLife research paper on which this eLife digest is based: “Human cardiac fibroblasts adaptive responses to controlled combined mechanical strain and oxygen changes in vitro” (March 18, 2017).
