Technique Visualizes and Protects Insulin Cell Transplants

Researchers have found a way to overcome a major stumbling block to developing successful insulin-cell transplants for individuals suffering from type I diabetes.

Traditional transplant of the cells, followed by necessary immune-suppressing agents, has had highly variable results, from well to poorly tolerated. Part of the problem, according to the researchers from Johns Hopkins University (Baltimore, MD, USA), is an inability to track the cells (pancreatic beta cells) once they are inside the body.

Now a new technique encapsulates the insulin-producing cells in magnetic capsules, using a U.S. Food and Drug Administration- (FDA)-approved iron compound with an off-label use, which can be monitored by magnetic resonance imaging (MRI). The agent, evaluated in laboratory pigs and diabetic mice, also simultaneously avoids rejection by the immune system, probably a major reason for transplant failure. The study was published in the online August 1, 2007, issue of the journal Nature Medicine.

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. This could solve the mystery of why current transplantation techniques work only for so long, stated one of the study's authors, Aravind Arepally, M.D., assistant professor of radiology and surgery at Hopkins.

Type I diabetes--the most common childhood type of diabetes--causes a person's immune system to destroy the pancreatic beta cells that make insulin. Without insulin, blood sugar levels can become dangerously high and lead to complications that include blindness or kidney failure. Precise monitoring of blood sugar levels paired with insulin injections can control the condition, but transplanting healthy beta cells holds more promise for the moment-to-moment fine-tuning of insulin levels, according to Dr. Arepally.

To address both of these challenges, the research team captured beta cells in tiny porous capsules made from a mixture of alginate, a sticky substance derived from seaweed, and Feridex, a magnetic iron-containing material visible under MRI. They then used a machine that dribbles 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.

The investigators first transplanted magnetocapsules into the abdomens of lab mice modified to develop diabetes. Blood sugar levels in the animals returned to normal within one 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 imitate 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, instead of the usual pancreatic home of beta cells, because it contains many blood vessels that can deliver insulin rapidly to the rest of the body.

The pigs underwent MRI and blood tests three weeks after magnetocapsule transplantation. The MRI scans revealed that the magnetocapsules remained intact in the liver, and blood tests demonstrated that the cells were still secreting insulin at levels considered functional in people.


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