Stories about: William Pu

Can we teach heart cells to grow up?

normal and mutant cardiomyocytes
A mutant heart muscle cell (in green) surrounded by normal cells. The mutant cell lacks Srf, a master maturation gene. It is unable to grow in size and lacks the fine membrane invaginations that help coordinate muscle contractions (appearing as vertical striations in the normal cells). (IMAGE: GUO Y; ET AL. NAT COMMS 9 #3837 (2018).]

Scientists around the world have been trying to replace damaged heart tissue using lab-made heart-muscle cells, either injecting them into the heart or applying patches laced with the cells. But results to date have been underwhelming.

“If you make cardiomyocytes in a dish from pluripotent stem cells, they will engraft in the heart and form muscle,” says William Pu, MD, director of Basic and Translational Cardiovascular Research at Boston Children’s Hospital. “But the muscle doesn’t work very well because the myocytes are stuck in an immature stage.”

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A tissue engineered heart ventricle for studying rhythm disorders, cardiomyopathy

a tissue engineered heart ventricle
(Luke MacQueen and Michael Rosnach/Harvard University)

While engineered heart tissues can replicate muscle contraction and electrical activity in a dish, many aspects of heart disease can only adequately be captured in 3D. In a report published online yesterday by Nature Biomedical Engineering, researchers describe a scale model of a heart ventricle, built to replicate the chamber’s architecture, physiology and contractions. Cardiac researchers at Boston Children’s Hospital think it could help them find treatments for congenital heart diseases.

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Tissue models of heart disease provide testing ground for treatments

Pink heart circuit board EKG-shutterstock_322058528Scientists are now able to create cardiac heart muscle cells from patients with heart disease. But cells alone aren’t enough to fully study cardiac disorders — especially rhythm disorders that require the activity of multiple cells assembled into tissues.

William Pu, MD, of Boston Children’s Hospital’s Heart Center and his team are honing the art of modeling heart disease in a dish. With an accurate lab model, they hope to test drug therapies without posing a risk to living patients (or even live animals).

Together with researchers at Harvard’s Wyss Institute, Pu’s lab recently modeled a rare rhythm disorder called catecholaminergic polymorphic ventricular tachycardia (CPVT). CPVT is a dangerous disease in which the heart’s rhythm can suddenly jolt abnormally without warning. Undetectable on a resting electrocardiogram (EKG), CPVT does not affect patients at rest. However, exercise or emotional upset trigger high levels of adrenaline, which can lead to life-threatening arrhythmia, cardiac arrest and possibly sudden death.

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Meet the researcher behind “heart on a chip”

Pu and wife and waterfallFrom a series on researchers and innovators at Boston Children’s Hospital.

With all of the recent buzz about precision medicine, it’s no wonder that William Pu, MD is gaining recognition for his innovative application of stem cell science and gene therapy to study Barth syndrome, a type of heart disease that severely weakens heart muscle. Pu’s research was recently recognized by the American Heart Association as one of the top ten cardiovascular disease research advances of 2014.

Can you describe your work and its potential impact on patient care?

We modeled a form of heart-muscle disease in a dish. To do this, we converted skin cells from patients with a genetic heart muscle disease into stem cells, which we then instructed to turned into cardiomyocytes (heart-muscle cells) that have the genetic defect. We then worked closely with bioengineers to fashion the cells into contracting tissues, a “heart-on-a-chip.”

How was the idea that sparked this innovation born?

This innovation combined the fantastic, ground-breaking advances from many other scientists. It is always best to stand on the shoulders of giants.

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‘Heart on a chip’ suggests a surprising treatment for a rare genetic disease

heart chip BarthIt was the variability that intrigued pediatric cardiologist William Pu, MD, about his patient with heart failure. The boy suffered from a rare genetic mitochondrial disorder called Barth syndrome. While he ultimately needed a heart transplant, his heart function seemed to vary day-to-day, consistent with reports in the medical literature.

“Often patients present in infancy with severe heart failure, then in childhood it gets much better, and in the teen years, much worse,” says Pu, of the Cardiology Research Center at Boston Children’s Hospital. “This reversibility suggests that this is a disease we should really be able to fix.”

Though it needs much more testing, a potential fix may now be in sight for Barth syndrome, which has no specific treatment and also causes skeletal muscle weakness and low white-blood-cell counts. It’s taken the work of multiple labs collaborating across institutional lines.

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