'Natural' pacemaker from stem cells may replace electronics

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The Independent Online

Biological heart pacemakers made from human embryo cells have been successfully tested in pigs, raising the possibility that tissue transplants could replace electronic pacemakers.

Biological heart pacemakers made from human embryo cells have been successfully tested in pigs, raising the possibility that tissue transplants could replace electronic pacemakers.

Because they would be natural, the cell implants would need no power source and, over time, would integrate naturally with the heart. They could even be genetically engineered or manipulated to enhance or alter their function, say scientists.

Although many obstacles need to be overcome before biological pacemaker cells can be used in practice - such as ensuring they cannot form tumours - the proof-of-principle research, carried out by a team in Israel, is a landmark.

The pacemaker cells were derived from stem cells extracted from early-stage donated human embryos.

Such embryonic stem (ES) cells are unprogrammed "mother" cells able to become any type of body tissue, including nerves, organs, skin and heart muscle.

Although some find their use controversial, many scientists believe they hold the promise of revolutionary new cures and treatments for diseases ranging from Parkinson's to diabetes.

In the new study, scientists from Israel and the United States grew ES cells in the laboratory and chemically coaxed them into becoming cardiomyocytes, the standard muscle cells of the heart. The cells formed three-dimensional clusters called embryoid bodies, parts of which were seen to beat spontaneously in the same way as a normal heart muscle.

Cells from the beating areas were first tested on pacemaker heart tissue taken from rats. Within 24 hours of grafting the myocytes on to the tissue, both sets of cells were contracting with a synchronous rhythm.

Next, the cells were injected into the hearts of pigs which had had surgery to produce an abnormally slow heart rate.

The transplanted human cells acted like a biological version of an electronic pacemaker, generating a new rhythm in the hearts of 11 out of 13 animals.

In five pigs, the activity was limited to isolated beats or short runs. But in the remaining six, the hearts developed a "regular, sustained and haemodynamically stable rhythm", the scientists reported in the journal Nature Biotechnology.

The team, led by Dr Lior Gepstein, from the Technion-Israel Institute of Technology in Haifa, wrote: "These results suggest the potential utility of these cells to serve as a biological pacemaker and for cardiac regenerative medicine in general."

The scientists said pacemaker cells could theoretically be made in unlimited numbers, and could easily be engineered to give them different functions.

That could offer relief for hundreds of thousands of people around the world who now use artificial pacemakers to regulate the beating of their heart because the normal cells that generate the rhythm work irregularly, or they have a break in the cell system of the heart used to spread the natural pacemaking nerve signal.

Artificial pacemakers can bring a host of problems along with their life-saving capability. The electronic systems work by giving the heart muscle a regular electrical stimulus to make it beat. But mobile phones and other equipment can interfere with their function.

KEEPING PACE

* 1950: First external pacemaker designed and built by Canadian electrical engineer John Hopps; it used a lead attached at one end to the heart and the other to a mains supply.

* 1958: First implantation into a human, Arne Larsson, by a Swedish team. The device, the size of a hockey puck, failed after three hours; a second then lasted for two days. Mr Larsson survived until December 2001 after having received 22 different pacemakers. * 1960: First totally implantable pacemaker: the first patient died of other ailments nine months later. The battery could last up to 18 months.

* 1965: New techniques allowed pacemakers to be installed by sliding a wire along a vein without opening the chest cavity - and thus without general anaesthetic

* 1975: Lithium-iodine batteries meant pacemakers could last up to 10 years.

* 1980s: New "rate responsive" versions could detect exertion and speed up or slow the heart.

* 1990s: New systems stored data about the heart's behaviour to be downloaded by the patient's cardiologist.

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