Bioengineering the Heart, Piece by Piece

It looks like heart muscle and beats like heart muscle, but this small patch of pulsing cardiac tissue didn’t come from a living animal. It was created by researchers in the U-M Artificial Heart Laboratory. Their ability to grow bioengineered heart muscle from cardiac cells in the lab represents a major step toward the long-term goal of creating replacement parts for damaged human hearts.

Ravi Birla with Louise Hecker, a graduate student in the Section of Cardiac Surgery. Birla and Hecker are senior author and lead author, respectively, on the paper, “Engineering the heart piece by piece: state of the art in cardiac tissue engineering,” published in the March 2007 issue of Regenerative Medicine. Photo: Scott Galvin

“Tissue engineering is a rapidly evolving field, and cardiovascular tissue is one of the most exciting areas, but also one of the most challenging,” says Ravi Birla, Ph.D., who directs research in the Cardiac Surgery Artificial Heart Laboratory. “Although tremendous technological challenges remain, we are now at a point where we can engineer first-generation prototypes of all cardiovascular structures.”

This means that heart attack survivors could one day have patches of laboratory-grown muscle implanted in their hearts to replace areas that died during the attack. Children born with defective heart valves could get new ones that grow permanently in place, rather than having to be replaced every few years. And people with clogged or weak blood vessels might get a “natural” replacement grown in a tissue incubator called a bioreactor.

While it will be years before bioengineered heart muscle can be used in human beings, U-M scientists have started experiments to transplant it into the hearts of rats with heart attack damage to see if the new tissue heals the damage.

Among the hurdles still to be overcome: determining which types of cells hold the most potential and finding the best way to grow those cells to form viable cardiac tissue that is strong, long-lasting and structured, at a cellular level, like natural tissue.

U-M scientists and biomedical engineers work together in the Artificial Heart Laboratory to compare the effectiveness of different platforms used to engineer functional heart muscle. With the right growing conditions, they can encourage cardiac muscle cells to begin producing the molecules they need to communicate and connect with other cells, and to generate the extracellular matrix or scaffold that supports cells in tissue.

“We’re interested in creating models of the different components of the heart one by one,” says Birla. “It’s like building a house — you need to build the separate pieces first. Once we understand how these models can be built in the lab, then we can work toward building a bioengineered heart.”

The U-M is applying for patent protection on its new bioengineering technology and is looking for a corporate partner to help bring this technology to market.

—Kara Gavin and Sally Pobojewski

For an expanded version of the story:
www.med.umich.edu/opm/newspage/2007/enginheart.htm

www.med.umich.edu/opm/newspage/2006/behm.htm

A Patch for Damaged Heart Muscle

Adapted from Regenerative Medicine 2 (2), 125-144 (2007) with permission of Future Medicine Ltd.

When plaque deposits form inside coronary blood vessels, they can restrict the flow of blood to an area of heart muscle, which can cause a myocardial infarction, or heart attack. Lacking oxygen and nutrients from blood, that part of the heart muscle will die (dark area). This weakens the heart’s ability to pump blood efficiently.

To repair the damaged heart muscle, U-M researchers take muscle cells from somewhere else in the animal’s body and remove immature satellite cells from the muscle sample.

The satellite cells are placed on a porous biodegradable scaffold to help them grow into the specific size and shape required.

The cells are grown inside a bioreactor that simulates conditions inside the body.

When the tissue-engineered patch is ready, researchers implant it over the damaged heart muscle. As muscle cells in the patch grow, they fill in and become part of the animal’s heart, restoring its normal pumping ability.