How stem cells help repair hearts


Study suggests they trigger an immune response.


Stem cells are being used to help heart attack victims, but we don’t really know what their impact is. 

WITTHAYA PRASONGSIN / GETTY IMAGES

By Paul Biegler

The controversial use of stem cells to help patients recover from a heart attack may work, but not because it grows new heart muscle.

Research in mice has found that injecting stem cells into the heart triggers an immune response that makes the scar stronger and the heart beat more forcefully.

The study, published in the journal Nature, suggests the current practice of injecting stem cells into a patient’s blood may not be optimal: direct injection into the heart could be more effective.

The team, led by Jeffery D Molkentin from the Cincinnati Children’s Hospital Medical Centre, US, wanted to resolve the thorny debate about whether stem cell therapy works after a heart attack and, if so, how.

In this microscopic histology image, macrophage immune cells (in red and green) flock to the injured region of a damaged mouse heart three days after researchers injected adult heart stem cells within the yellow dotted area.

Cincinnati Children's

Heart attacks happen when a coronary artery gets blocked and starves oxygen to a zone of heart muscle. The damaged area heals up with a scar, which means the heart doesn’t pump so well.

The result can be fluid build-up on the lungs and shortness of breath – your classic heart failure.

For decades, the mainstay of treatment has been drugs, which restore normal heart function in up to 40% of people.

But more recently stem cells – taken from the person’s heart or bone marrow – have been injected into the bloodstream in the hope they will make their way to the heart and form new heart muscle.

Despite numerous trials, however, evidence of benefit is sparse. The European Society of Cardiology recently concluded “the early promise of cell therapy has not yet been fulfilled”.

Nonetheless, 61 US businesses reportedly offer the treatment, which has not been approved by the US Food and Drug Administration for heart failure. Hence the urgent need for clarity on what the stem cells actually do. To find out, Molkentin’s team induced heart attacks in a group of eight-week-old mice.

A week later they injected one of four treatments straight into the heart: live stem cells (taken from either heart or bone marrow); dead stem cells; a drug called Zymosan that causes an immune reaction; and saltwater as a control.

Then they put the injured heart through a series of tests to check its mechanics.

The live stem cells, they found, did improve heart function. But there was a catch. So did the dead stem cells. And Zymosan worked best of all.

What was going on?

The researchers found the stem cells weren’t forming new heart muscle. Instead they were triggering an influx of immune cells, the soldier cells that fight infection but also heal injuries.

Those immune cells, called macrophages, were transforming the heart scar – causing cells known as fibroblasts that make the scar to, in effect, “muscle up”.

“The innate immune response acutely altered cellular activity around the injured area of the heart so that it healed with a more optimised scar and improved contractile properties,” says Molkentin.

When the team gave the mice a drug to suppress the immune response, the ability of stem cells and Zymosan to repair the heart was lost.

Crucially, the team’s use of direct injections into the heart could, if the results translate to people, overcome failings in existing human research.

“Most of the current trials were also incorrectly designed because they infuse cells into the vasculature,” says Molkentin.

“Our results show that the injected material has to go directly into the heart tissue flanking the infarct [damaged] region. This is where the healing is occurring and where the macrophages can work their magic.”

Contribs paulbiegler 2.jpg?ixlib=rails 2.1
Paul Biegler is a philosopher, physician and Adjunct Research Fellow in Bioethics at Monash University. He received the 2012 Australasian Association of Philosophy Media Prize and his book The Ethical Treatment of Depression (MIT Press 2011) won the Australian Museum Eureka Prize for Research in Ethics.
  1. https://www.nature.com/articles/s41586-019-1802-2
  2. https://www.sciencedirect.com/science/article/abs/pii/S0033062017300634
  3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5866934/
  4. https://academic.oup.com/eurheartj/article/37/23/1789/1748947
  5. https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2645145
  6. https://jamanetwork.com/journals/jama/fullarticle/2728902
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