June 25, 2001 Under a $1.86 million grant from the National Institutes of Health, researchers at the University of Illinois at Chicago and Loyola University Medical Center are growing lifelike cardiac tissue for possible use in the scaffolding and repair of damaged heart cells.
The work is expected to have wide application in studying and eventually treating heart disease, the number one cause of death in the United States. Heart disease causes more than 41 percent of all deaths in the United States, with an average of 950,000 deaths annually.
The model heart tissue, a prototype of which has already been developed at UIC, will enable researchers to examine the chemical and physiological causes of heart failure. It may also one day be used in tissue engineering, to replace sections of damaged organs.
"Unlike a mechanical heart, cellular repairs would last forever," said Brenda Russell, professor of physiology and biophysics at the UIC College of Medicine.
Efforts began three years ago to create heart tissue in the laboratory that would act in many ways like a living heart. "The heart is a difficult organ to study," Russell said. "If you surgically intervene in a living animal with a defective heart, most of the other critical systems, like the lungs and kidneys, shut down. The animal dies. We needed a way to study the heart without the animal attached so that we could start and stop the heart to analyze conditions present when it failed."
Creating lifelike heart tissue from cardiac cells was technologically challenging. "Isolating cells from a heart and growing them in a standard laboratory petri dish is like taking an egg and cracking it into a frying pan," said Russell. "The yolk, or nucleus, sits on top and the white (the cardiac muscle protein) spreads out on the bottom of the pan."
"In other words, it's no longer a rope-like contracting fiber because it has nothing to attach to," Russell added. "As a result, it no longer works the way it should, and you can't study normal function. Moreover, laboratory petri dishes are flat-nothing like the real heart in terms of chemistry and microarchitecture."
In 1998, Russell began collaborating with Tejal Desai, assistant professor of bioengineering at UIC. Using molding techniques for which a patent has been filed, Desai was able to build "scaffolds" about an eighth of an inch in length that were nontoxic, optically clear, and capable of being stretched.
These scaffolds, or platforms, made from silicone polymers, allowed the researchers to study the grooves, pegs and bumps of heart tissue. Moreover, the surface of the scaffolds could be mechanically manipulated to mimic the pumping of heart cells.
"I knew we could produce small features," Desai said. "But I wasn't certain whether we could create them in materials that cells would grow on."
The final phase of the project involved sticking heart cells firmly to the slippery silicone surfaces of the scaffolds so that the mechanical activity could be mimicked in the laboratory. Luke Hanley, associate professor of chemistry and bioengineering, applied a process to link polypeptides to the silicone surfaces, fusing the cells to facilitate growth into healthy tissue.
According to Russell, the results were immediate and dramatic. "The cells behaved completely differently than on a flat surface," Russell said. "They migrated, found a micro projection, or a peg, and attached to it. More than 90 percent of the cells attached to a peg and stayed attached when mechanically pulsed."
Russell and her colleagues believe that their work is a breakthrough that could lead to the implantation of cardiac cells, or tissue engineering, to treat heart disease, although such therapy is probably a decade away. Under the NIH grant, Dr. Allen Samarel, professor of medicine and physiology at the Cardiovascular Institute of Loyola University Medical Center, will lend a clinical perspective to the project. Using genetic engineering techniques, he hopes to stimulate the growth of cardiac tissue on the textured membranes created at UIC.
"Now we can see what heart cells need chemically, mechanically and physiologically. If you don't understand that, you can't repair or replace them," Russell said.
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