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Promising Cell Transplantation after Heart Attack

Implanted \'spare cells\' prevent life-threatening cardiac arrhythmia in mice

Scientists from the University of Bonn, together with US colleagues, have achieved a sensational step forward in cardiac infarction research. In the coming issue of the journal 'Nature' they report about an experiment in which they implanted embryonic heart cells in mice after a heart attack. These test animals were protected against life-threatening cardiac arrhythmia. These so called ventricular tachycardias are the most common cause of death after a heart attack.

During a heart attack, irreparable damage is done to the heart muscle as a result of defective circulation. The feared consequence is what is known as ventricular tachycardias and the ventricular fibrillation that results from that. In this case, the hollow muscle's contraction is not coordinated and contracts at a high pulse rate. The frequency can reach more than 300 beats per minute. This condition is life-threatening because the blood cannot be pumped effectively via the blood circulation.

By implanting embryonic myocardial cells, this risk can apparently be drastically reduced, at least in mice. These are the results of scientists from the universities of Bonn, Cornell and Pittsburgh, published in the journal 'Nature'. The scientists treated mice after a heart attack with these cells and then tried to cause ventricular tachycardias by means of electrical stimulation. Only with slightly over one third of the mice did this arrhythmia occur just as rarely as with thoroughly healthy rodents.  By contrast, with untreated mice after a heart attack this ratio was almost 100 per cent.

A few thousand cells are sufficient

Replacing the dead heart tissue with new muscle cells is not a completely new idea. Up to now, the doctors focused especially on the reconstruction of the muscular function. After all, several hundred million muscle cells perish during a heart attack. The result is often heart failure, which can also be fatal. 'This weakness of the cardiac muscle cannot be resolved with spare tissue, even today,' Professor Bernd K. Fleischmann from the Institute of Physiology 1 explains. 'Too few implanted cells actually take on a permanent muscular function. For the prevention of cardiac arrhythmia, even a few thousand cells seem to be sufficient.'

With the skeletal muscular cells which were used for the therapy up to now, that actually does not work. 'They do not reduce the risk of a ventricular tachycardia. The opposite is true: the severity of the cardiac arrhythmia even increased in our study when we used skeletal muscular cells,' the Bonn cardiologist Professor Thorsten Lewalter emphasises. The reason for this is that for an ordered contraction it is important that the cells in the heart muscle communicate with another. To a certain extent, they pass on the 'pulse signal' to their neighbours for this. 'Real' heart muscle cells naturally have a special information channel for this purpose. We're talking about a cellular protein called Connexin 43. 'We were able to show that the embryonic myocardial cells which we implanted synthesise this protein Connexin 43, thereby allowing the electrical signal to be coupled into the infarction scar,' the heart surgeon Dr. Wilhelm Röll and physiologist Dr. Phillip Sasse explain.

New therapeutic approach

Scientists from the Institute of Genetics were successful in changing skeletal muscular cells in such a way that they also produced Connexin 43. The researchers also successfully tested these cells on mice that had had a heart attack. The risk level of a ventricular tachycardia fell to a level similar to that in healthy animals. This discovery potentially opens the door to a completely new therapeutic approach. With humans it is nevertheless not possible, for ethical reasons, to make use of embryonic heart muscle cells. 'But you could use stem cells from the leg muscle of a heart attack patient and  install the gene for Connexin 43 in them,' says Professor Michael I. Kotlikoff from Cornell University in Ithaca. 'These modified cells could be then implanted in the damaged heart.'  Rejection of the cells is unlikely in this case since the body would be dealing with its own (albeit genetically upgraded) cells. Bernd Fleischmann also talks about an important intermediate stage but urges caution about inflated hopes. 'Our results are valid for mice hearts,' he clarifies. 'Whether it works this way with humans has yet to be seen.'

The fact that the study was so successful was also due to the interdisciplinary nature of the project. With the Institute of Physiology 1 at the Life&Brain Centre, the Departments of Cardiosurgery and Internal Medicine II, as well as the Institutes of Genetics and Pharmacology, five research groups were involved in Bonn alone.

Contact:
Professor Bernd K. Fleischmann
Institute of Physiology 1, Life&Brain Centre, University of Bonn
Telephone: +49 (0)228 6885-200
E-mail:
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