Model of left ventricle of the heart could be used to study heart disease

Bioengineers in the US have successfully built a 3D beating model of the left ventricle; one of the four chambers in the heart, representing a major step towards recreating a model of the whole human heart.

The bioengineered 3-D model of the human left heart ventricle was developed by researchers at Harvard University in the US and could be used to study diseases, test drugs and develop patient-specific treatments for heart conditions such as arrhythmia.

The tissue is engineered with a nanofiber scaffold seeded with human heart cells. The scaffold acts like a 3D template, guiding the cells and their assembly into beating ventricle chambers. This allows researchers to study heart function using many of the same tools used in hospitals such as ultrasound.

“Our group has spent a decade plus working up to the goal of building a whole heart and this is an important step towards that goal,” said Professor Kit Parker, the Tarr Family Professor of Bioengineering and Applied Physics at the Harvard John A. Paulson School of Engineering and Applied Sciences and senior author of the study.

“The applications, from regenerative cardiovascular medicine to its use as an in vitro model for drug discovery, are wide and varied.”

The research was a collaboration between SEAS, Wyss, Boston Children’s Hospital and the Harvard Stem Cell Institute (HSCI).

“The long-term objective of this project is to replace or supplement animal models with human models and especially patient-specific human models,” said Luke MacQueen, first author of the study and postdoctoral fellow at SEAS and Wyss.

“In the future, patient stem cells could be collected and used to build tissue models that replicate some of the features of their whole organ.”

Professor William Pu, the Director of Basic and Translational Cardiovascular Research at Boston Children’s Hospital and co-author of the paper said, “an exciting door is opened to make more physiological models of actual patient diseases. Those models share not only the patient mutations, but all of the genetic background of the patient.”

The researchers also exposed the tissue to isoproterenol, a drug similar to adrenaline, and measured as the beat-rate increased just as it would in human hearts. They also poked holes in the ventricle to mimic a myocardial infarction and studied the effect of the heart attack in a petri dish that resulted.

To better study the ventricle over long periods of time, the researchers built a self-contained bioreactor with separate chambers for optional valve inserts, additional access ports for catheters and optional ventricular assist capabilities.

Using human cardiomyocytes [muscle cells that make up the heart muscle] from induced stem cells, the researchers were able to culture the ventricles for six months and measure stable pressure-volume loops.

“The fact that we can study this ventricle over long periods of time is really good news for studying the progression of diseases in patients as well as drug therapies that take a while to act,” said MacQueen.

Next, the researchers aim to use patient-derived, pre-differentiated stem cells to seed the ventricles, which would allow for more high-throughput production of the tissue.

“We started by learning how to build cardiac myocytes, then cardiac tissues, then muscular pumps in the form of marine organism mimics, and now a ventricle,” said Prof Parker. “Along the way we have elucidated some of the fundamental design laws of muscular pumps and developed ideas about how to fix the heart when these laws are broken by disease. We have a long way to go to build a four-chamber heart but our progress is accelerating.”

This research ‘A tissue-engineered scale model of the heart ventricle,’ was published in the journal Nature Biomedical Engineering.