Harvard University researchers have bioengineered a three-dimensional model of a human left heart ventricle that 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 ventricle chambers that beat in vitro. This allows researchers to study heart function using many of the same tools used in the clinic, including pressure-volume loops and ultrasound.

The research is published in Nature Biomedical Engineering.
"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 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."

Parker is also a Core Faculty Member of the Wyss Institute for Biologically Inspired Engineering at Harvard, the Harvard Stem Cell Institute and the Harvard Materials Research Science and Engineering Center.

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."

"An exciting door is opened to make more physiological models of actual patient diseases," said William Pu, the Director of Basic and Translational Cardiovascular Research at Boston Children's Hospital, a Professor of Pediatrics at Harvard Medical School, Principal Faculty member of HSCI and co-author of the paper. "Those models share not only the patient mutations, but all of the genetic background of the patient."

The key to building a functional ventricle is recreating the tissue's unique structure. In native hearts, parallel 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.

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