HSCI bioengineer and cardiologist collaborate to design a radically improved model of the heart
By Jessica Lau
Researchers use heart cells in the laboratory to study heart disease and test potential new therapies. Many of the heart disease models they use are cells that are grown in flat layers. But the contractions and electrical signals in these cell layers are far removed from three-dimensional heart chambers, which pump blood with different volumes and pressures.
To address this problem, Kevin Kit Parker, Ph.D. and William Pu, M.D., Principal Faculty members at the Harvard Stem Cell Institute (HSCI), joined forces to make laboratory heart models more physiologically relevant to patients with disease. For the past few years, they have been combining their expertise in different areas to create improved models of the human heart.
In their latest study, published in Nature Biomedical Engineering, Parker and Pu built a three-dimensional model of a heart ventricle — the main pumping chamber of the heart — that combined engineered nanofibers with stem cell technology. Luke MacQueen, a postdoctoral fellow in Parker’s Disease Biophysics Group, was the lead author on the study.
First, the researchers built a scaffold by spinning nanofibers into the shape of a heart ventricle. Next, they added heart muscle cells obtained from rats or differentiated from human induced pluripotent stem cells. The resulting three-dimensional heart model was around the size of a rat ventricle. It contracted to move fluid in and out of the chamber successfully.
To create a proof-of-concept disease model, the researchers injured the engineered ventricle to mimic structural arrhythmia — a disease where abnormalities in heart structure result in irregular heartbeats.
In the future, stem cells derived from patients with heart disease could be used to make engineered ventricles, so that the models capture the exact genetic background and mutations of the patients.
“The Disease Biophysics Group has been focused towards building a heart for over a decade,” said Parker. “We’ve spent considerable time understanding cardiac myocytes as building materials, developing new methods for textile manufacturing, and practiced our craft by building biohybrid mimics of marine organisms that pump like the heart. Along the way we have learned quite a bit about the fundamental laws of muscular pumps and tested our ability to design and build muscular pumps.
“There is much more to do, but we are opening a chapter in our quest to build a heart now that many of our tool sets and capabilities are merging,” said Parker.
“Our projects combine Kit Parker’s bioengineering with my lab’s heart disease cells,” said Pu. “The seeds for this collaboration were planted through HSCI — the community was how we first learned about each other’s work.”
Parker, the corresponding author of the study, is the Tarr Family Professor of Bioengineering and Applied Physics at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS). Pu is the Director of Basic and Translational Cardiovascular Research at Boston Children's Hospital (BCH) and a Professor of Pediatrics at Harvard Medical School.
MacQueen L.A. et al. (2018). A tissue-engineered scale model of the heart ventricle. Nature Biomedical Engineering. DOI: 10.1038/s41551-018-0271-5
Harvard SEAS News (2018). A 3-D model of a human heart ventricle.
BCH Vector blog (2018). A tissue engineered heart ventricle for studying rhythm disorders, cardiomyopathy.