Off-label use of MR contrast agent Feridex promises not only to visualize insulin-producing cell transplants but help protect them, at least temporarily, against attack by the recipient’s immune system.
Off-label use of MR contrast agent Feridex promises not only to visualize insulin-producing cell transplants but help protect them, at least temporarily, against attack by the recipient's immune system.
Johns Hopkins University research on animals has documented the benefits of this agent, approved by the FDA to detect and evaluate liver lesions and, therefore, available to physicians for clinical use. The effects of the agent, however, may be short-lived.
Animal studies in which the agent provided a protective barrier against the immune system, as well as an aid for visualizing the cells, showed benefits for only a few months. The use of Feridex might, however, help tissue-match recipients with prospective donors and, through MR, identify whether immunosuppressive drugs will be effective.
To date, transplanted pancreatic beta cells have been well to poorly tolerated, according to the researchers. Part of the problem, the Hopkins team reports, is an inability to track the cells once they're inside the body. A technique for coating these cells with the iron compound allows them to be tracked using MR.
The preclinical research, published online this week in Nature Medicine, demonstrates that encapsulating these cells and then transplanting them into swine and diabetic mice not only makes them visible on MR but prevents rejection by the immune system, likely a major reason for transplant failure, according to Dr. Aravind Arepally, an assistant professor of radiology and surgery at Hopkins.
"We're really excited because we can track where we put the cells and make sure their protective housing stays intact and that the cells don't move," he said. "This could solve the mystery of why current transplantation techniques work for only so long."
Type 1 diabetes, the most common childhood form of the disease, occurs when the immune system destroys the pancreatic beta cells that make insulin. Careful monitoring of blood sugar levels paired with insulin injections can manage the condition, but transplanting healthy beta cells could be a cure.
Current experimental cell transplantation techniques are done "naked and blind," according to coauthor Jeff Bulte, Ph.D., a professor of radiology and chemical and biomolecular engineering at Johns Hopkins. The unprotected transplanted cells are vulnerable to immune system attack, and they cannot be seen once transplanted, making it impossible for researchers to monitor their status.
Addressing both challenges, the research team captured beta cells in tiny porous capsules made from a mixture of seaweed-based alginate and Feridex. They then encapsulated individual islet clusters, each containing about 500 to 1000 insulin-producing beta cells in the mixture, which hardened into a so-called magnetocapsule measuring about 1/128 of an inch. The tiny spheres have nanoscale pores big enough to let the insulin out while keeping immune system agents from getting in.
When transplanted into the abdomens of mice engineered to develop diabetes, the magnetocapsules within a week brought blood sugar levels to normal, where they remained for more than two months.
To mimic human transplantation, the researchers implanted magnetocapsules into the livers of swine with guidance from MR fluoroscopy. The liver was chosen, rather than the pancreas, 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," Bulte said.