Scientists come closer to ‘mending broken hearts’ by using gene therapy to … – The Independent


Scientists have come a step closer to being able to repair the damage done by heart attacks, using a “cocktail of genes” to transform scar tissue into working heart muscles.

Novel techniques to “mend broken hearts” using gene therapy and stem cells represent a major new frontier in the treatment of heart disease.

In the latest breakthrough, achieved by researchers at the Gladstone Institute of Cardiovascular Disease in California, researchers were able to re-programme scar-forming cells into heart muscle cells, some of which were capable of transmitting the kind of electrical signals that make the heart beat, according to the latest issue of the Stem Cell Reports journal.

The same team demonstrated their technique last year in live mice, transforming scar-forming cells, called fibroblasts, into beating heart muscle cells, but this is the first time that human fibroblasts have been re-programmed in this way.

So far, the work with human fibroblasts has only been done in the lab, but it paves the way for new treatments for heart attack victims. Researchers said that the “cocktail of genes” used to regenerate cells could one day be replaced with “small drug-like molecules” that would offer safer and easier delivery.

“We’ve now laid a solid foundation for developing a way to reverse the damage [done by a heart attack] —something previously thought impossible — and changing the way that doctors may treat heart attacks in the future,” said Dr Deepak Srivastava, director of cardiovascular disease at the Gladstone Institutes. “…Our findings here serve as a proof of concept that human fibroblasts can be re-programmed successfully into beating heart cells.”

In 2012, Dr Srivastava and his team reported in the journal Nature that, by injecting three genes into the hearts of live mice that had been damaged by heart attack, fibroblasts could be turned into working heart cells.

The scientists attempted the same technique using human fibroblasts from foetal heart cells, embryonic stem cells and neonatal skin cells, injected with genes in petri dishes in the lab. An increased number of genes was required to transform the human cells, and the efficiency of the transformed cells was low, but the team were encouraged by the results.

“While almost all the cells in our study exhibited at least a partial transformation, about 20 per cent of them were capable of transmitting electrical signals – a key feature of beating hearts,” said Gladstone staff scientist Ji-dong Fu, the study’s lead author.

The number of people who survive heart attacks has increased considerably in recent decades. The British Heart Foundation (BHF) said earlier this year that 70 per cent of women and 68 per cent of men were now surviving. However, success in keeping people alive after a heart attack has led to a rise in the number of people suffering from the long-term after-effects, which include debilitating heart failure.

Heart failure occurs when the heart cannot function efficiently and can be caused by the damage done to the heart muscle during heart attack. More than 750,000 people in the UK suffer from heart failure.

Professor Jeremy Pearson, Associate Medical Director at the British Heart Foundation, said: “This research represents a small but significant step forward.  Last year these scientists had a real breakthrough when they turned fibroblasts – the cells that form scarred heart tissue – in the hearts of mice into beating heart cells, by injecting them with a ‘cocktail’ of different genes.

“Now, using a different combination of genes, they have managed to turn human fibroblasts into beating heart cells in a culture dish. This process is still a long way from the clinic, but advances like this bring us closer to the likelihood that we could one day use these techniques to mend human hearts.”

Source: Independent.uk

In vivo cardiac reprogramming contributes to zebrafish heart regeneration.


Despite current treatment regimens, heart failure remains the leading cause of morbidity and mortality in the developed world due to the limited capacity of adult mammalian ventricular cardiomyocytes to divide and replace ventricular myocardium lost from ischaemia-induced infarct1,2. Hence there is great interest to identify potential cellular sources and strategies to generate new ventricular myocardium3. Past studies have shown that fish and amphibians and early postnatal mammalian ventricular cardiomyocytes can proliferate to help regenerate injured ventricles456; however, recent studies have suggested that additional endogenous cellular sources may contribute to this overall ventricular regeneration3. Here we have developed, in the zebrafish (Danio rerio), a combination of fluorescent reporter transgenes, genetic fate-mapping strategies and a ventricle-specific genetic ablation system to discover that differentiated atrial cardiomyocytes can transdifferentiate into ventricular cardiomyocytes to contribute to zebrafish cardiac ventricular regeneration. Using in vivo time-lapse and confocal imaging, we monitored the dynamic cellular events during atrial-to-ventricular cardiomyocyte transdifferentiation to define intermediate cardiac reprogramming stages. We observed that Notch signalling becomes activated in the atrial endocardium following ventricular ablation, and discovered that inhibiting Notch signalling blocked the atrial-to-ventricular transdifferentiation and cardiac regeneration. Overall, these studies not only provide evidence for the plasticity of cardiac lineages during myocardial injury, but more importantly reveal an abundant new potential cardiac resident cellular source for cardiac ventricular regeneration.

Source: Nature

 

 

MRI detects early damage to chemotherapy child hearts.


Detecting early damage to a child’s heart following chemotherapy is possible using MRI scans, says a study from Canada.

Even when children’s heart function appeared to be normal, a new MRI method of mapping the heart was able to identify damage, University of Alberta researchers said.

chemo

A UK cardiologist said the impact of anthracycline treatment on children’s hearts was only now being understood.

Early detection was crucial, he said.

While chemotherapy treatment with anthracyclines is known to be effective against many types of cancer, it can lead to irreversible changes to the heart muscle which may not become apparent until several years after treatment.

Writing in the Journal of Cardiovascular Magnetic Resonance, the researchers said they performed MRI scans on children and young adults aged seven to 19 who were in remission following this type of treatment.

Using an emerging MRI method called T1 mapping, they said they were able to identify the early effects on patients’ hearts.

This happened even in children whose heart function appeared normal by ultrasound.

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Scanning the heart is more difficult than other organs because it is constantly in motion. But with modern scanners the images are fantastic.”

Dr Chris PlummerFreeman Hospital, Newcastle

Dr Edythe Tham and Dr Richard Thompson, who led the study, said: “In childhood cancer survivors, MRI changes were related to anthracycline dose given to the children.

“These changes are also mirrored by thinning of the heart wall and a reduction in the exercise capacity.”

Early protection

Dr Chris Plummer, consultant cardiologist at the Freeman Hospital in Newcastle, said the side effects of chemotherapy were well-known.

“Chemotherapy with anthracyclines is a very effective treatment for cancer but it can be quite toxic to the heart.

“We’ve known that for a long time but the number of children affected is only becoming appreciated now.

“We have to look for ways to protect the heart and intervene earlier when damage occurs.

“Waiting for visible heart damage to appear is too long to wait.”

But Dr Plummer said carrying out an MRI scan of a child’s heart was not an easy thing to do.

“Scanning the heart is more difficult than other organs because it is constantly in motion. But with modern scanners the images are fantastic.

“It’s the best way of looking at the structure and function of the heart – and it’s entirely safe.

“It is an excellent way of precisely monitoring heart function in children.”

Source: BBC