Building a better mouse test for bone and fat

2010-12-04T01:00:00Z 2011-03-14T09:20:53Z Building a better mouse test for bone and fatBy MARK ANDERSEN / Lincoln Journal Star JournalStar.com
December 04, 2010 1:00 am  • 

Grandma could divine the internal qualities of a fresh melon using only a few thumps. She would strum them like a Stradivarius.

Energy waves that penetrate the melon rind produce a range of hollow thumps if the fruit is newly ripe.

University of Nebraska-Lincoln researcher Shadi Othman thinks the principle -- substituting acoustic waves for thumps and high-energy magnetism for Grandma's ears -- could determine the finer qualities of bioengineered bone or fat growing inside of living mice, and eventually humans.

Like Grandma, he could learn what he needs to know about what's happening inside without picking up a knife, which would be a boon to more than just the expensive rodents in his lab.

Sonograms, X-rays and MRIs already can provide the basic shape, location and density of pea-sized lumps of experimental bone, but they reveal little about its boney qualities, its strength and flexibility.

Those are crucial measures, says researcher Angie Pannier.

Functional bone to replace parts worn by age, eaten by disease or shattered by accident -- that's pretty much the whole point of manufacturing bone in the first place.

Pannier and Othman, both assistant professors in the Department of Biological Systems Engineering at UNL, run East Campus labs focused on MRI and tissue engineering.

Using previously discovered processes, Pannier immerses adult stem cells extracted from bone marrow into a milieu of nutrients and genetic signals. Depending on the recipe, the cells usually transform into fat or bone.

The gelatin sponge that holds the cells determines the shape.

But that's not the cool part of this project, she says.

Engineered tissue emerged as a field 17 years ago, Pannier says, and by now, everyone expected there'd be more tissues than the small palette of tools available to clinicians.

The need for bone is obvious. Engineered fat would be useful for burn patients or for reconstruction after cancer surgeries.

Pannier knows she can make bone, or rather a grouping of bonelike cells, but bone isn't cement, she says. It's a living thing nourished by blood. It undergoes constant remodeling.

There's still a lot for researchers to learn.

And scientists have been hampered by the need to destroy their experiments to check their progress, she said.

That's what makes Othman's project cool, she says. They'll use something called magnetic resonance elastography, which employs mechanical waves and supercharged magnetic fields, to measure the bonelike qualities of their engineered bone, the fatlike qualities of their engineered fat, and they'll do it without cutting the melon.

The $500,000 9.4 Tesla MRI arrived at Othman's lab last December.

A typical hospital MRI generates a 1.5 Tesla magnetic field, although 3 Tesla machines are becoming common. The more power, the better the image quality and detail.

A coin-sized neodymium magnet generates 1.25 Tesla and can lift 20 pounds of iron. Researchers in the Netherlands harmlessly levitated a live frog in a 16 Tesla field.

The size of the engineered bone and fat samples, about 3 millimeters, dictates the need for such a strong magnetic field.

The first group of mice implanted with engineered tissue began to undergo weekly scans in June.

During the hourlong procedure, the mice are under anesthesia, wear ear plugs and receive oxygen. Their heart rate, temperature and breathing are monitored.

"If for any reason the mouse is not comfortable," Othman said, "we stop."

Tests on the first group ended in August, and new tests on another group of mice will begin soon.

The first results were as expected, Othman says.

"If this ... can do what we say it can do," Pannier said, "it could really improve tissue engineering."

Researchers have been looking for better ways to evaluate their experiments, she says. Othman brings a novel approach.

"Nobody," she said, "was trying MRE (magnetic resonance elastography)."

Reach Mark Andersen at mandersen@journalstar.com or call 402-473-7238.

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