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Injecting stem cells into the body may be the first hurdle in creating treatments for disease, but ensuring that the microscopic cells get to their intended destination also is an important step. Johns Hopkins scientist Jeff Bulte, Ph.D., has been studying how to noninvasively track the whereabouts of neural and cardiac stem cells after they are put into the body.
Jeff Bulte, Ph.D., professor
of radiology, biomedical
engineering, and chemical
& biomolecular engineering,
and director of the cellular
imaging section of the Institute
for Cell Engineering.
He uses ultra small molecules called nanoparticles to act as tracking devices for stem cells. The nanoparticles he created contain iron oxide, a magnetizer, which is visible through magnetic resonance imaging (MRI). Stem cells grab onto the nanoparticle and take it with them as they travel to the heart, spinal cord or brain.
So far, Bulte has been able to show that he can use MRI to track stem cells in mice, rats, pigs and dogs. MRI cell tracking studies have also been performed in humans, albeit not with stem cells but with immune cells used as cancer vaccine. He is now working on incorporating genetic instructions into stem cells to respond to specific radiofrequencies visible to MRI.
Bulte and colleagues also have developed methods for tracking cells by encapsulating them with an FDA-approved iron compound that can be tracked by MRI.
Current experimental cell transplantation techniques are done “naked and blind,” only lasting a short period of time, says Bulte, a professor of radiology, biomedical engineering, and chemical and biomolecular engineering at Hopkins. The unprotected transplanted cells are vulnerable to attack by the recipient’s immune system.
To address both of these challenges, the research team captured pancreatic islet beta cells—insulin producing cells—in tiny porous capsules made from a mixture of alginate, a gooey material made from seaweed, and Feridex, a magnetic iron-containing material visible under MRI. They then used a machine that oozes droplets of this mixture to surround and encapsulate individual islet clusters each containing about 500 to 1,000 insulin-producing beta cells. Once the cells are encapsulated, the shell hardens, creating a “magnetocapsule” that measures less than 1/128 of an inch across.
“They’re tiny spheres with nano-scale pores just big enough to let the good stuff out but keep the bad from getting in,” says lead author Brad Barnett, medical student and Howard Hughes fellow at Hopkins. The openings in the magnetocapsule are so small that the body’s immune system sentinels cannot reach and attack the transplanted cells.
The team first transplanted magnetocapsules into the abdomen of mice engineered to develop diabetes. Blood sugar levels in the animals returned to normal within a week and stayed that way for more than two months. In contrast, more than half of untransplanted diabetic mice died, and the rest had very high blood sugar levels.
To mimic human transplantation, the researchers then implanted magnetocapsules into the livers of swine with the help of MRI fluoroscopy, special reflective screens and a computer monitor that provided real-time imaging. The liver was chosen, rather than the usual pancreatic home of beta cells, because it contains many blood vessels that can deliver insulin quickly to the rest of the body.
The pigs underwent MRI and blood tests three weeks after magnetocapsule transplantation. MRI showed that the magnetocapsules remained intact in the liver, and blood tests revealed that the cells were still secreting insulin at levels considered functional in people.
“We hope that our magnetocapsules will make tissue-type matching and immunosuppressive drugs problems of the past when it comes to cell-based therapies for type 1 diabetes,” says Bulte.
–by Vanessa Wasta and Audrey Huang