Bioengineers Make Three Dimensional Living "Heart Patch"

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Main Category: Cardiovascular / Cardiology
Also Included In: Biology / Biochemistry;  Medical Devices / Diagnostics;  Stem Cell Research
Article Date: 12 Oct 2009 - 2:00 PDT

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By imitating the way embronic stem cells grow into heart muscle, bioengineers from the US say they have completed the first step toward growing a living three dimensional "heart patch" that has the potential to repair heart tissue. However, they stressed at this stage their experiment represents proof of principle and there is still a long way to go before such a patch could be implanted into human hearts damaged by disease.

The experiment was conducted by researchers in biomedical engineering in the Pratt School of Engineering at Duke University in Durham, North Carolina. They presented their results at the annual scientific meeting of the Biomedical Engineering Society in Pittsburgh on 8 October.

The bioengineers developed their own three dimensonal mold made of heart muscle cells or cardiomyocytes grown from mouse embryonic stem cells. The structure looks a little like one of those lattice-shaped small breakfast cereal squares known in the US as Chex, and in the UK as Shreddies.

The researchers varied the shape and length of the holes in the lattice to control the direction and position of the cells as they grew. They also created an environment very similar to that found in natural tissue: they enclosed the cells in a gel made of fibrin, a blood-clotting agent. The fibrin supported the cells, allowing them to grow in three dimensions.

An important discovery was that the cardiomyocytes only grew successfully in the presence of cardiac fibroblasts, a type of "helper" cell that makes up 60 per cent of all the cells in the human heart.

The new cells that grew on the mold showed two important properties of heart muscle cells: the tissue they formed contracted and conducted electrical signals.

One of the bioengineers, graduate student Brian Liau, who works in the laboratory of assistant professor Nenad Bursac at Duke's Pratt School of Engineering, told the press that:

"If you tried to grow cardiomyocytes alone, they develop into an unorganized ball of cells."

"We found that adding cardiac fibroblasts to the growing cardiomyocytes created a nourishing environment that stimulated the cells to grow as if they were in a developing heart," said Liau, explaining that when they tested the patch they found that because the cells lined up in the same direction, they were able to contract like native cells.

"They were also able to carry the electrical signals that make cardiomyocytes function in a coordinated fashion," he added.

Liau said they believe that by adding fibroblasts they provided signals like the ones that are present in a developing embryo. It is quite common for helper cells to do this in the development of mammals. For instance, explained Liau, nerve cells are sheathed by glia cells which help them grow and function properly.

Bursac said their experiment really just represents proof of principle and there were still many hurdles to overcome before patches could be implanted into humans to repair heart tissue damaged by disease.

"While we were able to grow heart muscle cells that were able to contract with strength and carry electric impulses quickly, there are many other factors that need to be considered," said Bursac.

Bursac said the fibrin acted as a structural material that allowed them to grow thicker, three-dimensional patches, an essential component of delivering therapeutic doses of cells. But after that the next major challenge, and it would be one of many, would be to establish a blood supply to feed the new tissue once in situ.

Another major challenge with growing human tissue would be that human cardiomyocytes tend to grow a lot slower than those of mice.

"Since it takes nine months for the human heart to complete development, we need to find a way to get the cells to grow faster while maintaining the same essential properties of native cells," said Bursac, adding that if they could also use the patient's own cells, then the patient's immune system would be unlikely to reject it.

Liau, Bursac and colleagues now plan to test the new model using non-embryonic stem cells.

The research was sponsored by the National Institutes of Health, the National Heart Lung Blood Institute and Duke's Stem Cell Innovation program.

"Engineering Functional Anisotropy of Myocardial Tissue by Hydrogel Micromolding."
W. Bian, B. Liau , and N. Bursac.
Presented at Biomedical Engineering Society Annual Meeting Held at David L. Lawrence Convention Center, Pittsburgh, PA, 7 - 10 October 2009.
Track: Cardiovascular Engineering, Cardiac Electrical Structure and Function, Podium Session: OP 8-3-4F, 8 October 2009.

Source: Duke University.

Written by: Catharine Paddock, PhD
Copyright: Medical News Today
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