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Diabetes Researchers Find the Grail

By Sean Henahan, Access Excellence

San Antonio, TX (6/11/00)- The Holy Grail of diabetes research, an unlimited source of functional, insulin-producing beta-cells is now a reality, announced researchers at the American Diabetes Association's 60th annual meeting. The new ability to produce these cells, missing in patients with insulin-dependent diabetes, offers the promise of effective treatment and possible cure for the disease without depending on the donation of organ tissue, always in short supply.

A research team from the University of California in San Diego reported the creation of an immortalized cell-line that produces the precious human beta-cells in virtually unlimited numbers. The finding couldn't come at a better time, as clinical researchers have also recently announced improved success with beta-cell transplantation in patients with Type I, insulin-dependent diabetes. The new laboratory technique could assure a reliable supply of the insulin-regulating cells for patients who need them.

left: Dr. Fred Levine and colleagues in the lab

"Even if you had unlimited success with tissue transplantation, there is simply not enough donor tissue to treat the millions of people who have diabetes. We have now been able to create an immortal human cell line, and have demonstrated in mice that these cells are functional when transplanted, secreting insulin in response to glucose stimulation.," said Fred Levine, M.D., Ph.D., associate professor at the UCSD Cancer Center and the Whittier Institute in San Diego, whose laboratory reported the successful results

The new cell line was created by hybridizing human beta-cells with an line of cancer cells, a standard approach for creating immortal, protein producing cells. It took the researchers eight years to develop the technique for making these particular cells. The research presented at the ADA conference involved studies with mice. In those studies, the experimental beta-cells responded to glucose by producing sufficient insulin in the animals. Human studies are still some years away, Levine cautioned.

Some 16 million people in the US alone have diabetes, primarily of the Type-II, non-insulin-dependent variety. If a sufficient supply of beta-cells were available, both Type I (insulin-dependent) and Type II patients could also benefit from cell transplantation.

Important Progress on the Transplant Front

transplant me!Until now, transplanting beta-producing cells into patients with diabetes has involved either transplanting a donor, islet-cell producing pancreas, or, direct infusion of islet-cells. These methods have been used with some success for several years, but were hampered not only by a shortage of cells for transplantation, but also by interaction with the patient's immune system requiring the use of immunosuppressive drugs. Researchers from Edmonton, Alberta, Canada reported important progress on the front recently with a modified approach. Developed by Dr. James Shapiro, the 'Edmonton Protocol' uses a novel steroid-free combination of three drugs--Tacrolimus, Sirolimus and Daclizumab--which together prevent rejection of the transplanted islets and also stops the autoimmune diabetes from returning. The protocol also uses more islets and transplanted them immediately rather than putting them in an incubator for several days after they are removed. That work is now being expanded to clinical trials across North America, under the auspices of the Immune Tolerance Network, a consortium of research centers.

right: a healthy islet cell (click for transplant animation)

Other approaches now being investigated in the area of islet-cell transplantation include the concomitant use of bone marrow stem cells during transplantation, the use of monoclonal antibodies to modulate the immune response, and the use of genetic engineering techniques to deliver other potentially useful anti-rejection proteins.

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