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August 16, 2001

"Computer chip-making technology aids research"

August 13, 2001

Equipment designed to fabricate computer chips can also make homes for living cells, scientists have learned, in a development likely to have a profound impact on medical research.

Cardiac researchers at the University of Illinois' Chicago campus have found they can isolate heart tissue cells on a three-dimensional platform and keep them upright and beating, much as the cells act when part of a living heart.

This is in dramatic contrast to what usually happens when lab workers try to isolate cardiac cells in a standard flat petri dish. In a flat dish, the cells that don't die will just flop over and spread like an egg cracked into a pan, said Brenda Russell, professor of biophysics at UIC.

"They don't do anything, so you can't use them to study function," she said.

Researchers like to isolate living cells in the lab because it gives them a quick, inexpensive way to do experiments. A certain kind of bacteria growing in a petri dish can be sprinkled with various substances to see which ones kill the bacteria quickest, for instance.

But scientists haven't been able to do that with heart cells. Instead they must use living animals for the first tests of possible new drugs to treat coronary maladies. It's expensive and time-consuming, said Russell, but for decades there has been no alternative.

That may soon change. Working with bioengineers and chemists, Russell has isolated coronary tissue cells from baby rats that act similarly to a living heart. The key is to construct a dish with tiny structures or pegs that give the cells something to grab onto so they can keep their shapes, she said.

"It had long been part of my wish list to have a dish with tiny pegs on it so I could see if the cells would behave differently," she said. "But I never knew how to get such a thing."

When she learned that a new colleague, Tejal Desai, an assistant professor of bioengineering, was making microscopic structures for other types of cells, Russell asked if Desai could craft something for cardiac cells.

"She did it and it worked the first time," said Russell. "Seldom in research does anything work the first time."

Desai and her students use equipment designed to fabricate silicon chips. But instead of silicon, they use biologically friendly materials such as silicone and silica. And rather than designing race tracks for electrons to whiz through, they're making tiny pegs for cardiac cells to grab.

Russell and Desai work with a chemist and a cardiologist to improve the miniscule cell habitats and make them more elaborate to better mimic the conditions within a beating heart.

It is very much like building a zoo for cells.

When wild animals were captured and put into sterile cages with steel bars, they became listless and did little more than lie around or pace back and forth. But when their zoo environment mimics nature with trees, bushes, running water and other amenities, the animals perk up.

Cells seem to be the same way. The researchers are feeling their way in an effort to provide the equivalent of bushes, trees and streams for cells living in the three-dimensional habitats.

Luke Hanley, an associate professor of chemistry, rearranges the surface chemistry of the cardiac cell habitats, inserting small analogs of proteins and otherwise modifying shapes on a tiny scale to see how this changes the behavior of the cells.

Because they work on such a tiny scale, Hanley and his colleagues spend a lot of time checking how they've modified things and how the cells react.

Better growth environment

One way to check for progress is to analyze the makeup of cardiac cells exposed to the new environment, said Dr. Allen Samarel, a cardiologist on the faculty of Loyola University Medical Center.

Working cardiac cells contain about 20 percent of a protein called myosin, which means "muscle motor," while the same cells lying flat in a petri dish are about 2 percent myosin, Samarel said.

"Our cells are much better than 2 percent," he said. "But they're not the same as cells in a beating heart. We're not halfway there yet, but we're getting better. This is really basic research."

Applying chemicals and electricity to the environment, the scientists can cause several cells to pump together in a dish, and as they manipulate the environment, the researchers learn more about how the cells work.

Their first goal is to create artificial environments where cardiac cells will behave as much as possible as they do in the beating heart. That would enable drug researchers to screen for heart drugs without having to use rats and mice as they do now, and it would give scientists a way to learn much more about cell behavior.

"We can look at a cell stretching in a dish and change just a single gene to see how that modifies behavior," Russell said.

Besides helping to develop new cardiac drugs, attaining knowledge of cell behavior is necessary for one of science's long-term goals, which is to grow heart cells artificially and use them to replace tissue damaged by a heart attack.

A stem cell example

This is an application of stem cell research, the general cell-therapy field that has received much public attention in recent months. Stem cells are fundamental cells that can become specialists like nerve cells, muscle cells and so on.

Some experimenters have injected stem cells into cardiac muscle and seen a few become cardiac cells, said Samarel, which in principle shows that such an idea can work.

"But just injecting stem cells into a coronary muscle leaves a lot to chance," he said. "Any form of replacement therapy would require you to amplify the number of stem cells and differentiate them into cardiac cells outside the body before injecting them into the heart."

Providing an environment where such manipulation could take place is what Desai and Hanley are doing, but each new iteration of a cell habitat is costly and time-consuming.

"We're looking for ways to scale this up and to cut costs," said Hanley, "so that you could make specialized chips more quickly."

Working with a $1.86 million grant from the National Institutes of Health, the Illinois team continues to refine its cell habitats. The effort is still in an early stage, but it has generated some outside attention.

Desai said companies that make lab equipment have inquired about her three-dimensional cell environments.

"We haven't even gotten to the point of applying for a patent and we've heard from some people who say they might want to license the technology," she said. "That is very unusual."

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