Stem cell treatment can help damaged hearts regenerate tissue. By Michael Lim

AGE does not spare one from the ravages of heart damage. Whether it be the young woman in her 30s whose heart was severely damaged by a virus infection and was so badly incapacitated that without a heart transplant, she would perish in less than a year. Or the gentleman in his 60s whose heart attack so severely impaired his heart function that he was asked to consider a heart transplant.

Young or old, severe heart pump deterioration can occur in both groups. Despite advances in medicine, the prognosis of patients who have been hospitalised for heart pump failure have continued to be poor, with a five-year mortality that is close to 50 per cent.

While an artificial heart can sustain a heart for years, the cost can be prohibitive as it runs into hundreds of thousands of dollars, not to mention the physical limitations associated with carrying a large battery pack. Worldwide, donor hearts for heart transplantation are a scarce resource. Furthermore, heart transplants have a limited span and it is not infrequent for the patient to require a subsequent repeat heart transplant.

Magic bullet

For decades, many physicians have embarked on the search for the magic bullet to regenerate damaged heart muscle. From time immemorial, physicians have been taught in medical schools to believe that once the heart muscle is damaged, it cannot regenerate.

This “truth” which has been taught to medical students through the decades came under challenge in 2001 when a group of researchers led by Beltrami published a study in the New England Journal of Medicine to demonstrate that after a heart attack, heart muscle cells could regenerate.

Stem cells, early cells which have the ability to grow into different types of mature cells, have become the buzzword and many see this as a “magic bullet”.

In the last decade, many researchers have been looking for the magic bullet and have used a range of stem cells from different sources. Early researchers have tried using early bone marrow cells to regenerate damaged hearts.

In 2003, an important ground-breaking study by Beltrami’s group were able to isolate from the hearts of rats, a population of heart stem cells that were self-renewing and had the ability to grow into heart muscle cells, blood vessel muscle cells and cells that line the lumen of blood vessels. These heart stem cells were identified by the presence of a special marker, tyrosine kinase c-kit (c-kit positive).

It meant that adult mammalian hearts had a reservoir of early cells which had the ability to multiply and grow into different types of cells which are essential for regeneration of damaged heart tissue.

It took several years before these animal data could be translated into human studies. The first clinical study in humans, SCIPIO, was published by Bolli in Lancet in 2011 where heart stem cells were used for the treatment of heart muscle damaged by previous heart attacks. During open heart bypass surgery, tissue from the right upper heart chamber was removed by the surgeons and heart stem cells were isolated and grown from the removed tissue.

Few months later, the cultivated heart stem cells were infused through the heart arteries or grafts supplying the scarred heart muscle. Those receiving stem cell infusion showed improvement in heart pump function, functional capacity and quality of life.

The next important step was to understand how the heart muscle regenerated and what happens to scar tissue. Last month, Bolli’s group published an important paper in the Circulation journal, which helped us to understand the mechanism for regeneration of damaged heart muscle and scarring, following the injection of stem cells.

Using pigs, they induced a heart attack by occluding a heart artery and waited three months for scar tissue to form before infusing c-kit positive heart stem cells into the vessel supplying the scarred heart tissue. Microscopic examination of the pigs’ hearts subsequently showed that there were new cells that were forming new heart muscle and blood vessels in the scarred area.

What was also observed was that there was also less scar tissue in the heart treated with stem cells compared to those that were not treated with stem cells.

This study confirmed the mechanism by which injected heart stem cells can regenerate scarred heart muscle and sets the stage for further studies to use heart stem cells to repair damaged heart cells in humans.

Self-repair

The mention of stem cells excites both doctors and patients alike. However, the generic term of “stem cells” encompasses a wide variety of cells from different sources which may or may not have useful clinical application or efficacy.

As the long and arduous route taken by the researchers have shown, many potential lines of heart stem cells for regeneration of damaged heart muscle have fallen into disuse or remained in the realm of research, and the years of laborious research have finally led to the identification of the c-kit positive heart stem cell which is the most promising of all the heart stem cell lines.

These research findings have significant implications for those who have damaged heart muscles as a result of blocked heart arteries, virus infection or chemotherapy-induced damage.

By harvesting c-kit positive heart stem cells from one’s own body, it may be theoretically possible to regenerate one’s own damaged heart muscle.

For those whose lives are caged in by the limitations of their impaired heart function, these findings bring new hope that in the not-too-distant future, regenerating one’s own damaged heart from self-harvested stem cells is a routine reality.