Cell-Tuning for stuttering Hearts

20. February 2008

Deadly cardiac arrythmias are the most feared complication of an acute myocardial infarction. Scientists now succeeded to prevent ventricular tachycardia from mice by embryonic cells. And even better: It worked with genetically pepped-up skeletal muscle cells as well.

It's the nightmare of any cardiologist: A patient with an acute myocardiac infarction was saved and successfully treated. And just when it looks like the worst is over – all of a sudden, ventriuclar tachycardia set in. And a patient seemingly ready for after-care is a case for the ICU – in the best possible scenario. “Such cardiac arrythmias after an infarct develop in the border area between infarct tissue and normal myocardium”, explains Professor Bernd Fleischmann of the Institut für Physiologie at the Life&Brain-Zentrum in Bonn/Germany during the interview with DocCheck Newsletter. Here, and not in the regular nervous conduction system, suddenly electric excitations are produced which do not belong there.

Stem cells curb arrythmias

Together with colleagues of the US universities Cornell und Pittsburgh, Fleischmann now tested a method fit to solve the issue of ventricular tachycardia after an infarction at least on mice: The injection of embryonic cardiac myocytes. The scientists reported in the professional magazine Nature about it. They initiated heart attacks and treated the mice afterwards with embryonic cells. “Technically this is a cardiac surgical operation. The embryonic cells are injected directly into the damaged tissue and the adjacent areas”, says Fleischmann.
The results were amazing: After the operation, only every third animal suffered from cardiac arrythmias – about the same rate as found in healthy mice. In the comparison group, practically every animal without cell therapy developed ventricular tachycardia. One of the interesting things in this experiment: Relatively few cells were sufficient to achieve the effect of a stabilized rhythm. Although millions of cardiac myocytes perish during an infarction: “We need only about 100,000 cells to achieve the positive effects on the cardiac rhythm”, says Fleischmann. Researchers trying to stop heart failure after a myocardiac infarction with stem cells, have to start thinking in completely new dimensions.

It might work without embryos

At least in German, the therapy with embryonic cells has a certain taste to it and many consider that getting into the way for a potential clinical application. But the scientists have made yet another experiment which might solve this issue. They applied skeletal muscle cells in an otherwise identical procedure. At first it did not work: The cells were missing a cell protein named Connexin 43 which is essential for electric cell communication. “We were able to show that the embryonic cardiac mycocytes we implanted started building that Connexin 43. In addition they launched the electric signal in the infarction scar”, elucidates Dr. Wilhelm Röll, cardiac surgeon in Bonn. For that reason, the scientists used a transgenic mouse model where the Connexin 43 is expressed in the skeletal muscle as well. And behold: This time the cardiac arrhythmias were controllable effectively with the skeletal muscle cell injections as well!
That at least implies a therapy approach for a potential application on human beings: Stem cells could be taken form the skeletal muscles of a cardiac infarction patient. The cells could be changed by planting the gene for Connexin 43 and afterwards be implanted in the damaged heart where they could exercise their protecting effects. But Fleischmann warns of early hopes here. “The heart of the mouse is different from the human heart in many regards. The next step is to repeat the experiments on large animals more similar to the human being. Only then we can start considering an application of the method on men”.

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