Engineering heart tissue presents particularly tough problems for researchers, since the heart is an active organ, contracting rhythmically to pump blood at high forces throughout the body. Scientists at MIT have found a new material on which to grow heart cells that better mimics the properties of heart muscle. The material, reported in Nature Materials this week, could be used to grow patches of tissue to repair heart injuries and defects, or to screen heart drugs in the lab.
Growing a heart: In this confocal microscope image, living heart cells (in green, with blue nuclei) grow on a honeycomb-like scaffold (in blue) that helps arrange the cells in a pattern that more closely resembles the structure of heart muscle.
Several labs have been working on ways to grow heart tissue by seeding living heart cells or stem cells onto artificial scaffolds. These scaffolds are designed to support the cells initially and then degrade over time as the cells form their own external support structures, leaving functioning tissue behind. But, says George Engelmayr, a postdoctoral fellow in the Harvard-MIT Division of Health Sciences and Technology who led the study, the scaffolds designed for other kinds of tissues did not have the right mechanical properties for heart tissue. Heart tissue must be flexible enough to change shape as the heart contracts, but also strong enough to withstand the intense forces generated by these contractions.
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So, the researchers used a polymer originally developed in the lab of Robert Langer at MIT. “It’s elastic like a rubber band,” Engelmayr says, so it can withstand repeated stretching while only gradually losing strength as it degrades. Furthermore, the polymer can vary in stiffness, depending on how long it has been cured with heat, allowing the team to vary its mechanical properties with precision.
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Cells of the heart are arranged in specific directions, which allows the heart chambers to be stiffer and stronger around their circumference than in the longitudinal direction. The researchers designed the scaffold to encourage cells to align themselves in the same direction to better mimic this property of natural heart muscle tissue. Using a laser cutting technique, they created a pattern of oblong holes in the polymer; the result is a flexible, honeycomb-like structure that is stiffer in one direction than another.
The researchers seeded small patches of the scaffold with heart cells from newborn rats and grew them for one week. They found that the mechanical and electrical properties of the engineered tissue varied in different directions. For instance, when the cells were lined up parallel to an electric field, they beat in sync more readily.
Frederick Schoen, a professor of pathology at Harvard Medical School who was not involved in the study, says that the MIT research offers a solution to a problem that has only recently been addressed by cardiac tissue engineers. Schoen says that, just as rowers line up in one direction to propel a boat forward, “all the heart muscle cells in a given region have to be lined up and contracting in the same direction” in order for the heart to beat efficiently. The honeycomb-like scaffold described by the MIT group represents a “substantial jump” toward that goal, Schoen says.
Ultimately, the goal is to create patches of tissue that can repair damaged areas of the heart better than current patches, which are made out of synthetic materials. Richard Weisel, a cardiac surgeon from University of Toronto, says that such patches are used during heart surgery in two major ways: to restore heart tissue in patients who have had damaged tissue removed after a heart attack, and to repair congenital heart defects in infants and children. But inert materials, while helpful, can’t act as part of the living heart and can lead to scarring over time. “If we had a biodegradable biomaterial, which had beating heart cells, we might be able to return function to that part of the heart,” he says.
But a major hurdle still must be crossed before heart tissue engineering becomes a reality: finding a reliable source of cells. While Weisel and other researchers have had luck coaxing adult stem cells from bone marrow and other tissues to turn into heart muscle cells, Lisa Freed, senior author of the Nature Materials paper, says that finding enough stem cells to generate tissue is still a practical problem. Another challenge is to expand this honeycomb scaffold to create thicker, larger pieces of tissue, which would be necessary to have practical uses in the clinic.
In the meantime, Freed believes that the technology could have a more immediate use as a better way to screen for heart drugs. She says that a three-dimensional scaffold of aligned cells offers a more true-to-life model for testing how drugs affect the beating heart than current methods that rely on cells cultured in a single layer.
