Monday, October 31, 2011

Zebrafish have capacity to regenerate their own hearts

The potential to regenerate organ tissue is exciting news as researchers around the world are developing techniques such as generating beating heart cells from stem cells. I had the opportunity to see this in action during a personal tour of the McEwen Centre for Regenerative Medicine and learned that stem cells are undifferentiated (or unspecialized) cells that are capable of renewing themselves indefinitely. This undifferentiated state means that a single stem cell has a unique capability to grow and generate a wide variety of specialized cell types (e.g., muscle cells, neurons, heart muscle cells, etc) under the right physiological conditions.

How a fish can teach us survival
Zebrafish have a rare capacity to regenerate their own hearts if they get damaged. Now scientists hope to learn from them.

Zebrafish are not just for brightening aquariums, they are key to research. Photograph: Alamy
The British Heart Foundation turned 50 earlier this year and launched its Mending Broken Hearts Appeal – one of its most ambitious projects ever. The goal is to spend £50m ($80.57 million) on research that could begin to literally mend broken hearts in as little as 10 years.

Hope for success rests partly on the amazing zebrafish, which have the ability to regenerate heart muscle – something that tens of thousands of people in the UK living with debilitating heart failure caused by a heart attack can't do. By unlocking the biological secrets of the zebrafish, scientists funded by the Mending Broken Hearts Appeal aim to identify and harness the key genes and chemical messengers that allow the fish to regenerate heart muscle, and find a way to help human hearts damaged by heart attacks heal themselves.

Without this vital research, the growing number of patients surviving heart attacks will remain without hope of an end to the debilitating symptoms of heart failure, such as breathlessness, tiredness, palpitations, swollen ankles, lack of appetite, anxiousness and depression. Drugs and surgery can help alleviate symptoms, but currently the only cure for heart failure is a heart transplant. And even if a donor is found, a heart transplant may not fully restore quality of life for recipients who require a lifetime of immunosuppressant drugs to prevent organ rejection.

How much better it would be to be able to regenerate healthy heart tissue and replace heart muscle destroyed by heart attacks. The zebrafish is already providing vital clues about how this could be done in human hearts. If part of its heart is damaged, it can repair it in a matter of weeks, just like we are able to mend a broken bone.

Because zebrafish are transparent early in their life cycle, it is relatively easy for researchers to see their hearts and blood vessels grow. Their hearts begin to develop after just 12 hours, and they reach adult size – about 3cm long – in about three months, so they can provide quick research results.

Dr Tim Chico, consultant cardiologist at the University of Sheffield, whose work is partly funded by the British Heart Foundation (BHF), explains: "The same pathways and genes that made my heart and your heart are responsible for switching on heart development in zebrafish. At that fundamental level we share more common mechanisms than you might imagine.

"We have a library of many thousands of compounds that might be the next best drug. With zebrafish we can very quickly screen them to see if the compounds have an effect.

"We can switch off genes and see how the zebrafish regrows vessels to repair damage. If we could switch the right genes on in humans then we could live longer and survive better after a heart attack."

By spending £50m ($80.57 million), the BHF aims to fund world-leading scientists in stem cell research, regenerative medicine and developmental biology to find ways to repair or replace damaged or dead heart tissue with new, healthy, functioning heart tissue.

"The aim of the Mending Broken Hearts Appeal is to start early clinical trials within five years and full trials within another five so that in 10 years people with heart failure would have a brighter future," says the BHF's medical director, Professor Peter Weissberg.

Stem cells, for example, offer hope because they have the potential to turn into any specialist cell. Scientists think they can harness stem cells from elsewhere in the patient's body to repair damaged heart muscle – or find out what can trigger stem cells already present in the heart to repair themselves. read more.

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