Wednesday, December 19, 2012

Genetic modification yields biological pacemakers

Our heart pumps around blood by beating around 50-60 times per minute. It is controlled by electrical signals that come from the brain, and they have the capability to make the heart go faster or slower, depending on the required blood flow. If those signals do not work anymore, the heart stops. In the case of heart failure, patients often get an implant that we call a pacemaker. This is a device that provides rhythmic electrical signals in order to keep the heart going. Obviously, implanting an electric device has its downsides. A study by the Cedars-Sinai Heart Institute shows that we may actually be able to recruit the body's own cells as pacemakers.

When the required signal for heart contraction is given, all heart muscle cells involved need to be in sync: only if all cells respond to the incoming signal at the same time it is possible to direct the blood flow. If heart cells responded randomly, things would get rather messy. To keep things in sync, there are channels that connect the cells, so that an incoming signal spreads itself rapidly throughout the heart. Normally, there are two areas (the SA and AV node) from which the signal spreads, as visualized below.
If either the SA node or AV node fails, an alternative signalling system is required to keep the heart from failing. As said, there are specific electrical devices, pacemakers, developed for the heart. However, the Cedars-Sinai Heart Institute came up with an alternative method. They recruited ordinary heart cells to become highly specialized pacemaker cells. Because the SA and AV node also consist of a bunch of specialized cells, this is basically a biological alternative to a pacemaker, and resembles the natural situation more closely.

In order to get the heart cells to perform their duty as pacemaker cells, the scientists had to modify their behaviour. They managed to do so by modifying the cells with just a single gene, called Tbx18. After this particular gene became active in the heart cells, they started behaving exactly like cells in the SA node. This is quite remarkable: normally, in order to generate a specific type of cell, it is necessary to use reprogrammed stem cells. Being able to transfer ordinary heart cells into a real pacemaker cell with just a single gene is quite amazing.

In terms of behaviour, the newly generated pacemaker cells look just like their ordinary counterparts. Obviously, this does not mean that they will perform as required in the body. To this end, clinical studies are required to see whether these pacemaker cells can actually keep the heart going in patients that require it. The scientists think that future therapy could consist of an injection that contains the Tbx18 gene, which is consequently taken up by the heart cells and expressed. It could prove to be a simple alternative to pacemaker devices.

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