Jun 10 2011

Repairing the Heart

One of the probable early applications of stem cell technology to repair damaged or diseased tissue is heart failure. The heart is essentially a big muscle. There is some complexity to its structure, in terms of how the chambers and vessels are arranged, and the electrical system that coordinates how each chamber pumps in succession. But if this structure is largely intact, and only muscle is damaged (most commonly from an infarct – a heart attack), then all that is needed is for more cardiac muscle cells to grow to replace the damaged ones. Heart cells automatically synchronize their contractions, so new heart muscle should pump right along with the others without a problem.

There are now two approaches that I have read about to repair damaged heart muscle in order to improve cardiac function. Researchers are looking at injecting stem cells into the heart that will then differentiate into cardiac muscle. Researchers have already tested the treatment in humans – injecting a patient’s own stem cells into the heart. They report an average of 9% increase in ejection fraction, and a range of 0-20%.

A 9% improvement may not sound like much, but for patients with heart failure this can be huge. A healthy adult has a significant reserve of cardiac function. The heart can work much harder when running a marathon or climbing stairs, than when just sitting or walking. But heart failure patients typically have little or no reserve – their heart is working at maximal capacity with just sitting or light movement. This, of course, is very limiting. Any increase in heart function therefore translates into greater endurance and comfort, even for everyday activity.

This treatment is not yet mainstream, and is still considered experimental, but it seems poised to become a standard treatment for heart failure.

Another line of stem cell research involves cardiac stem cells that are already present in the heart – so-called epicardium derived progenitor cells. These cells exist in the lining of the heart – the epicardium. Like many stem cells in the body, they are dormant in adults (probably to reduce the chance of cancer). Researchers are looking at using a hormone drug (thymosin beta 4)  to stimulate these stem cells into becoming active again. Once active they will migrate into the heart and repair damage.

This research is only at the mouse level, but the early results are promising. They found that if the drug is given to mice before a heart attack, then after the heart attack the progenitor cells will migrate into the heart, replace damaged heart muscle, thicken the heart walls, and reduce scarring. They report an increase in ejection fraction of 25% in some test animals – a massive improvement.

The catch is that these results have only been seen in animals. When similar therapies translate to humans the improvement is much less impressive. But as I stated above, even a 5% or so improvement in ejection fraction can make a significant difference to heart function and quality of life. It’s also possible that this therapy can be combined with injectible stem cells to get an additive effect.

The other limitation, which you may have noticed in the description above, is that the drug needs to be given before the heart attack. This is not something that can be injected or taken as a pill in the emergency room to an acute heart attack victim. This is a significant limitation. Still, the drug might be given daily to those at high risk of heart attack, so that if they do have a heart attack their recovery will be better. But this will not help those who have a heart attack without much warning. Also, taking this medication daily for months or years is likely to have greater potential for side effects than if it just needed to be taken for a short period of time during or after a heart attack.

The researchers estimate that it will be about 10 years before thymosin beta 4 is approved for use (if they get enough money to continue the research, of course). Ten years means they have no idea, in my opinion. There are still significant hurdles to cross, and they might not be crossed. I hope this approach proves useful, but at this point it’s a bit of a long shot.

It’s good that this research is being approached from different angles, because you can never tell which one will pay off. I would put my money on injectible stem cells at this point, but thymosin beta 4 (or a similar drug) may also prove effective some day.

It’s also interesting to think what effect this would have on heart transplants. Many heart transplants are performed for heart failure – hearts that are just too far gone to function adequately. If more failing hearts could be repaired with stem cells, that would mean the need for fewer heart transplants.

Researchers are also working on ways to use stem cells to grow artificial hearts. This research is still in its infancy. The method they are looking at now is starting with a denuded scaffolding – taking a heart, stripping away all the cells so that you are left with just the connective tissue. Then using stem cells to grow a new heart on the connective tissue. This approach is interesting, but has significant limitations – you still need a donated heart to provide the scaffolding (although this can be an animal heart).

This research is also too far off to predict if or when it will pan out. What I find intriguing is that using stem cells to repair a failing heart is almost the same as building a new heart, but instead of building it on a scaffold and then transplanting it into a patient – you just build it on the patient’s existing heart scaffolding, by repairing their own heart.

Whichever one of these research approaches bears fruit, it does seem that repairing hearts is the low hanging fruit of stem cell therapy.

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