The National Institutes of Health (NIH) has awarded researchers at Rice University and the Texas Heart Institute (THI) a $1 million Challenge Grant to refine cell-tracking nanotube technology that could make magnetic resonance imaging (MRI) up to 40 times more sensitive than existing MRIs and help guide stem cells within the human body to repair damaged hearts.
“This is an exciting and important step that will help meld two very promising technologies developed at our partnering institutions in a way that holds a lot of lifesaving promise,” said James Willerson, MD, THI president and a partner in the stem-cell research.
The grant will help perfect technology based on an ultrasensitive class of MRI contrast agents invented at Rice in 2005. Prescribed for about a third of all MRI patients today, contrast agents increase the sensitivity of MRI scans and make it easier for doctors to deliver a diagnosis. The most effective and common of these clinical agents contain a toxic metal called gadolinium, which is sequestered by wrapping the metal in organic molecules called chelates.
In Rice’s new contrast agents, the gadolinium is encased inside hollow tubes of pure carbon, called nanotubes, to eliminate the metal’s toxicity. These ‘gadonanotubes’ are at least 40 times more effective at boosting MRI signals than traditional gadolinium contrast agents.
“There’s a great deal of interest in using stem cells to regenerate damaged heart tissue, but there hasn’t been a really effective way to track the cells in vivo [within the body] and test their effectiveness,” said gadonanotube inventor Lon Wilson, professor of chemistry at Rice. “Gadonanotubes may be what’s needed because they are small enough to internally label individual cells with a large number of nanotubes and sensitive enough to track the cells in real time.”
In addition, the gadonanotubes make the labeled cells highly magnetic so that it may be possible to steer the cells in vivo with an external magnetic field. This may aid in keeping the stem cells in a desired place for the several weeks it takes them to differentiate into heart muscle cells.
With the new grant, researchers at Rice and the THI will label stem cells with gadonanotubes and attempt to use the cells to regenerate damaged heart tissue in pigs. The team will use MRI to track the cells and judge their effectiveness.
“At THI, we are very excited to work in collaboration with Rice,” said Emerson Perin, MD, principal investigator on the Challenge Grant, director of clinical research for cardiovascular medicine at THI and medical director of THI’s Stem Cell Center. “It’s very exciting to utilize nanotechnology as a completely novel way for us to further understand stem cell therapy through imaging and tracking stem cells injected into the heart.”
“We’re very optimistic that this work may allow us to direct stem cells to a desired position and retain them in the heart with an external magnet,” said Dr. Willerson. “That would be a major milestone.”
Challenge Grants are part of the NIH’s stimulus funding initiative. The agency allotted $200 million from the American Recovery and Reinvestment Act (ARRA) for Challenge Grants, which promote advances in high-impact areas like regenerative medicine.
The NIH received a staggering 20,000 grant proposals for ARRA funding, and Wilson said the gadonanotube proposal was ranked within the top 2 percent. He also said Rice graduate student Lesa Tran deserves a large amount of the credit for that. Tran, a third-year PhD student, helped invent gadonanotubes while working as an undergraduate intern in Wilson’s lab. In her graduate work, Tran splits her time between Perin’s and Wilson’s labs, where she’s helped complete the groundwork for the NIH proposal under the direct supervision of Maria da Graça Cabreira, senior research scientist of the Stem Cell Center.
“This grant is a real milestone for the project, and it’s a great testament to the hard work that Lesa and the rest of the team have dedicated to this project,” Wilson said.