3D is the big news in the world of TV this year and now even cell cultures are getting in on the act. A team of scientists has taken aim at a biological icon - the two-dimensional petri dish – and unveiled a new technique for growing 3D cell cultures. The new process uses magnetic forces to levitate cells while they divide and grow to form tissues that more closely resemble those inside the human body. This represents a technological leap from the flat petri dish and could save millions of dollars in drug-testing costs.
According its developers, the 3D technique is easy enough for most labs to set up immediately. To make cells levitate, the research team modified a combination of gold nanoparticles and engineered viral particles called "phage". This targeted "nanoshuttle" can deliver payloads to specific organs or tissues.
"There's a big push right now to find ways to grow cells in 3D because the body is 3D, 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 per drug."
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.
The new technique is an example of the innovation that can result when experts come together from disparate fields. Study co-author Tom Killian, associate professor of physics at Rice, 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 at the Koch Center, mentioned one day that he was developing a gel that could load cancer cells with magnetic nanoparticles, it led to a new idea.
"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, a start-up 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 3D medium produced proteins that were similar to those produced by gliobastoma tumors in mice, while cells grown in 2D did not show this similarity.
The researchers are now conducting additional tests to compare how the new method stacks up against existing methods of growing 3D cell cultures. They are hopeful that it will provide results that are just as good, if not better, than longstanding techniques that use 3D 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 3D microtissue structures. The method is fairly simple and should be a good point of entry in 3D cell culturing for any lab that's interested in drug discovery, stem cell biology, regenerative medicine or biotechnology."
The research is reported in Nature Nanotechnology.