Feridex (ferumoxides injectable solution) was the world’s first organ-specific MR imaging agent. Developed by Bayer for detection and evaluation of liver lesions, this agent is now being studied by scientists as a possible tracking agent and protector, to guard the pancreatic beta cells in type I diabetics who underwent islet cell transplant.
The press statement from Johns Hopkins explains:
Current experimental cell transplantation techniques are done “naked and blind,” only lasting a short period of time, according to co-author Jeff Bulte, Ph.D., a professor of radiology and chemical and biomolecular engineering at Hopkins. The unprotected transplanted cells are vulnerable to attack by the recipient’s immune system, and researchers cannot see the cells to figure out why they stop making insulin after a while.
To address both of these challenges, the research team captured beta 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 too 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 abdomens 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 provide 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.
“Getting the magnetocapsules into the right place requires hand-eye coordination normally required when playing video games,” says Arepally. The team threaded a long needle-like tube into a large vein near the upper thigh and guided the tube upward, across and into a neighboring blood vessel, ending in the body of the liver.
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.
Johns Hopkins Medical Institutions press release: New technique to ‘see’ and protect transplants successful in diabetic animal model …
Howard Hughes Medical Institute press release: Imaging Islet Cell Transplants …
Product page: Feridex …