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HOUSTON -- (March 15, 2010) -- The film "Avatar" isn't the only 3-D
blockbuster making a splash this winter. A team of scientists from
Houston's Texas Medical Center this week unveiled a new technique for
growing 3-D cell cultures, a technological leap from the flat petri dish
that could save millions of dollars in drug-testing costs. The research
is reported in Nature Nanotechnology.
The 3-D technique is easy enough for most labs to set up
immediately. It uses magnetic forces to levitate cells while they divide
and grow. Compared with cell cultures grown on flat surfaces, the 3-D
cell cultures tend to form tissues that more closely resemble those
inside the body.
"There's a big push right now to find ways to grow cells in 3-D
because the body is 3-D, and cultures that more closely resemble native
tissue are expected to provide better results for preclinical drug
tests," said study co-author Tom Killian, associate professor of physics
at Rice. "If you could improve the accuracy of early drug screenings by
just 10 percent, it's estimated you could save as much as $100 million
For cancer research, the "invisible scaffold" created by the
magnetic field goes beyond its potential for producing cell cultures
that are more reminiscent of real tumors, which itself would be an
important advance, said co-author Wadih Arap, professor in the David H.
Koch Center at The University of Texas M.D. Anderson Cancer Center.
To make cells levitate, the research team modified a combination of
gold nanoparticles and engineered viral particles called "phage" that
was developed in the lab of Arap and Renata Pasqualini, also of the Koch
Center. This targeted "nanoshuttle" can deliver payloads to specific
organs or tissues.
"A logical next step for us will be to use this additional magnetic
property in targeted ways to explore possible applications in the
imaging and treatment of tumors," Arap said.
The 3-D modeling raises another interesting long-term possibility.
"This is a step toward building better models of organs in the lab,"
The new technique is an example of the innovation that can result
when experts come together from disparate fields. Killian studies
ultracold atoms and uses finely tuned magnetic fields to manipulate
them. He had been working with Rice bioengineer Robert Raphael for
several years on methods to use magnetic fields to manipulate cells. So
when Killian's friend Glauco Souza, then an Odyssey Scholar studying
with Arap and Pasqualini, mentioned one day that he was developing a gel
that could load cancer cells with magnetic nanoparticles, it led to a
"We wondered if we might be able to use magnetic fields to
manipulate the cells after my gels put magnetic nanoparticles into
them," said Souza, who left M.D. Anderson in 2009 to co-found Nano3D
Biosciences (www.n3dbio.com), a startup that subsequently licensed the
technology from Rice and M.D. Anderson.
The nanoparticles in this case are tiny bits of iron oxide. These
are added to a gel that contains phage. When cells are added to the gel,
the phage causes the particles to be absorbed into cells over a few
hours. The gel is then washed away, and the nanoparticle-loaded cells
are placed in a petri dish filled with a liquid that promotes cell
growth and division.
In the new study, the researchers showed that by placing a
coin-sized magnet atop the dish's lid, they could lift the cells off the
bottom of the dish, concentrate them and allow them to grow and divide
while they were suspended in the liquid.
A key experiment was performed in collaboration with Jennifer
Molina, a graduate student in the laboratory of Maria-Magdalena
Georgescu, an M.D. Anderson associate professor in neuro-oncology and
also a co-author, in which the technique was used on brain tumor cells
called glioblastomas. The results showed that cells grown in the 3-D
medium produced proteins that were similar to those produced by
gliobastoma tumors in mice, while cells grown in 2-D did not show this
Souza said that Nano3D Biosciences is conducting additional tests to
compare how the new method stacks up against existing methods of
growing 3-D cell cultures. He said he is hopeful that it will provide
results that are just as good, if not better, than longstanding
techniques that use 3-D scaffolds.
Raphael, a paper co-author, associate professor in bioengineering
and a member of Rice's BioScience Research Collaborative, said, "The
beauty of this method is that it allows natural cell-cell interactions
to drive assembly of 3-D microtissue structures. The method is fairly
simple and should be a good point of entry in 3-D cell culturing for any
lab that's interested in drug discovery, stem cell biology,
regenerative medicine or biotechnology."
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