Pathway to a cure  pg. 4

Last year in the United States, fewer than 2000 pancreases were recovered from donors. More than a million patients have type 1 diabetes.

“What you need is more tissue,” says Vanderbilt’s Wright. “Where do you get more tissue?”

Islet tissue could potentially come from another species, like pig, an area of research called xenotransplantation. Or insulin-producing cells could be grown in the laboratory, as genetically engineered cells or as the products of stem cells — embryonic or adult.

None of these options are clear-cut. Xenotransplantation must overcome concerns that pig-specific pathogens will infect the human recipients and potentially endanger public health. Genetic engineering of cells requires an appropriate cell starting point and knowledge of all the genes that are necessary for glucose-regulated insulin secretion. Likewise, turning stem cells into pancreatic cells requires identification of the complete set of factors that will elicit that conversion.

Securing a plentiful supply of islets or an alternative source of insulin-producing cells is just one of the hurdles looming for islet transplantation. Equally vexing is the long-term immunosuppression required to prevent attack of the transplanted cells.

Immunosuppressive drugs can blunt the immune system’s attack on transplanted tissues, as well as its attack on beta cells, the hallmark of type 1 diabetes. But even the Edmonton protocol’s newer, less toxic drug cocktail has “side effects that are not justified lifelong in juveniles,” says Dr. Allen Spiegel, former director of the National Institute of Diabetes & Digestive & Kidney Diseases. Immunosuppression puts patients at increased risk for infections of all types, for lymphomas and related malignancies, and for renal toxicity.

One appealing way to leap over this obstacle, Spiegel says, would be to induce “tolerance” of the transplanted cells, without requiring chronic drugs and without suppressing immunity overall. The Immune Tolerance Network, a $144 million project co-funded by the National Institute of Allergy and Infectious Diseases, the NIDDK and the JDRF, is working toward this goal. “There are some encouraging results, but a lot of work remains to be done,” Spiegel says.

It might also be possible to sheathe islets, or cell clusters, in materials that protect them from immune system attack but that allow passage of nutrients, glucose and insulin. Encapsulation strategies include ultrathin polymer membranes — microencapsulation — and porous matrixes with cells or islets dispersed inside — macroencapsulation.

“What we like about encapsulation is that it will eliminate the need for long-term immunosuppressive drug therapy,” says Taylor Wang, Centennial Professor of Mechanical Engineering and Applied Physics at Vanderbilt, and a former astronaut whose 1985 space shuttle experiments involving water and oil droplets turned out to have implications for encapsulating islets.

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