Photo courtesy of Luke MacQueen/Disease Biophysics Group/Harvard SEAS.

After more than a decade, scientists at Harvard University finally made a breakthrough in their efforts to create a heart. According to a study published in Nature Biomedical Engineering, the researchers successfully bioengineered a three-dimensional model of a human left heart ventricle. This important development brings them one step closer to their goal, creating a life-like model of a heart which could ultimately help scientists study heart disease, test drugs and develop patient-specific treatments for other heart conditions such as arrhythmia.

The key to building a functional ventricle is recreating the tissue’s unique structure. In human hearts, myocardial fibers act as a scaffold, guiding brick-shaped heart cells to align and assemble end-to-end, forming a hollow, cone-shaped structure. When the heart beats, the cells expand and contract like an accordion.

To make the ventricle, the researchers used a combination of biodegradable polyester and gelatin fibers that were collected on a rotating collector shaped like a bullet. Because the collector is spinning, all of the fibers align in the same direction.

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 ventricle chambers that beat in time with each other. This allowed researchers to study heart function in the lab, using many of the same tools used in the clinic, including pressure-volume loops and ultrasound.

After building the scaffold, the researchers cultured the ventricle with either rat muscle cells from rats or human heart muscle cells. Within three to five days, a thin wall of tissue covered the scaffold and cells were beating in synch. From there, researchers could control and monitor different aspects of the ventricle, such as pressure and volume of the beating.

To test the heart, the researchers exposed the tissue to isoproterenol, a drug similar to adrenaline, and measured as the beat-rate increased just as it would in human and rat hearts. The researchers also poked holes in the ventricle to mimic a heart attack and studied the effects in a petri dish. Using human heart muscle cells from induced stem cells, the researchers were even able to culture the ventricles for 6 months and measure stable pressure-volume loops.

“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, Ph.D., first author of the study and postdoctoral fellow at the Wyss Institute and SEAS. “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.”

While the applications for regenerative cardiovascular medicine are wide and varied, this advancement in their research is a step toward more accurate models of actual patient diseases.

In the future, we could see patient stem cells collected and used to build tissue models that replicate some or even all of the features of their entire organ.