Lab-grown artificial heart part has living cells, and it beats perfectly

Researchers plan to scale up their work in the future.
Ameya Paleja
The miniature left ventricle engineered in the labUniversity of Toronto

Researchers at the University of Toronto have grown a miniature model of the left ventricle of the human heart using living heart cells, a press release revealed on July 8. The heart part can beat like a regular heart and even pump fluid under laboratory conditions. 

The researchers chose to recreate the left ventricle since it is the heart's main chamber and pumps oxygenated blood into the aorta, which then carries it to the rest of the body. According to the World Health Organization, heart-related conditions are the leading cause of death globally.

Researchers worldwide are using a wide spectrum of approaches, from 3D printing the organ to transplanting new muscle cells, to help improve heart health, while also creating small lab-based models to trial drugs in development. Led by Milica Radisic, a professor at the Institute of Biomedical Engineering at the university, the research team created the ventricular tissue at a micron scale. 

How the researchers created the miniature heart

The researchers used tiny scaffolds made from biocompatible polymers to make their tissue in three dimensions instead of two dimension cultures that are conventionally used in laboratories. The scaffolds have grooves or mesh-like structures seeded with heart muscle cells and then allowed to grow in a liquid medium. 

As cells grew over time, they formed a tissue layer prompted by the underlying scaffold to grow in a particular direction. The researchers had designed the scaffold as a flat sheet of three mesh panels that could be rolled around a hollow polymer shaft after the cells had grown on the scaffold for about a week. 

The researchers also used electrical pulses to control how fast these muscles would beat. The end result was three layered heart muscles that could beat in unison and pump out fluid from one end. When comparing the tissue dimensions, the ventricle is about the size one would see inside the human fetus at about 19 weeks of gestation.  

"With these models, we can study not only cell function, but tissue function and organ function, all without the need for invasive surgery or animal experimentation," said Radisic. "We can also use them to screen large libraries of drug candidate molecules for positive or negative effects.”

 When the heart beats, the layers of muscle cells not only contract but also twist to enable more blood to be pumped out. By putting the three layers of cells at different angles to each other, the researchers could also replicate this capability. 

What happens next? 

Currently, the tissue can only create about 5 percent of the ejection pressure a human heart can create. The researchers are confident that they can scale up their tissue in the future. The current model has only three layers whereas human hearts have eleven layers of muscle cells. 

"We can add more layers, but that makes it hard for oxygen to diffuse through, so the cells in the middle layers start to die," said Sargol Okhovatian, one of the researchers involved in the project. "Real hearts have vasculature, or blood vessels, to solve this problem, so we need to find a way to replicate that". 

Additionally, the team intends to increase the cell density to increase the ejection volume and pressure of the organ. Recalling that the heart evolved into its current form over millions of years, Radisic said, "We’re not going to be able reverse engineer the whole thing in just a few years, but with each incremental improvement, these models become more useful to researchers and clinicians around the world."

The researchers published their research in the journal Advanced Biology.

Abstract

Despite current efforts in organ-on-chip engineering to construct miniature cardiac models, they often lack some physiological aspects of the heart, including fiber orientation. This motivates the development of bioartificial left ventricle models that mimic the myofiber orientation of the native ventricle. Herein, an approach relying on microfabricated elastomers that enables hierarchical assembly of 2D aligned cell sheets into a functional conical cardiac ventricle is described. Soft lithography and injection molding techniques are used to fabricate micro-grooves on an elastomeric polymer scaffold with three different orientations ranging from −60° to +60°, each on a separate trapezoidal construct. The width of the micro-grooves is optimized to direct the majority of cells along the groove direction and while periodic breaks are used to promote cell–cell contact. The scaffold is wrapped around a central mandrel to obtain a conical-shaped left ventricle model inspired by the size of a human left ventricle 19 weeks post-gestation. Rectangular micro-scale holes are incorporated to alleviate oxygen diffusional limitations within the 3D scaffold. Cardiomyocytes within the 3D left ventricle constructs showed high viability in all layers after 7 days of cultivation. The hierarchically assembled left ventricle also provided functional readouts such as calcium transients and ejection fraction. 

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