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Skin Cells are Reprogrammed to Produce Insulin

Proceedings of the National Academy of Sciences, August 31, 2009

Using ordinary skin cells derived from patients with Type I diabetes, scientists were able to reprogram the cells to create new cells that produce insulin. The announcement heralds a potentially revolutionary type of therapy for the millions of people who suffer from Type I diabetes.

In a procedure which is now commonly reproduced by stem cell scientists around the world, the researchers de-differentiated ordinary somatic (non-stem-cell) skin cells into a more primitive state, known as iPS (induced pluripotent stem) cells. In a new variaton on the theme, however, the iPS cells were then reprogrammed and re-differentiated into a new type of cell, one which resembles the insulin-producing beta islet cells of the pancreas. Specifically, the skin samples were obtained from two white males, one of whom had been diagnosed with Type I diabetes at 3 years of age, and the other of whom was first diagnosed at 21 years of age. Led by Dr. Douglas Melton, codirector of the Harvard Stem Cell Institute and a leading investigator at the Howard Hughes Medical Institute, the team of researchers reprogrammed the fibroblasts into iPS cells using 3 of the 4 genes that are commonly used for the iPS reprogramming procedure. Although the new cells do not produce insulin as efficiently as naturally occurring pancreatic cells do, nevertheless the new cells are responsive to changes in blood sugar levels. The procedure signifies an especially important accomplishment since the skin cells were not randomly taken from any donor but instead were specifically taken from patients who are suffering from Type I diabetes, thereby yielding a new type of cell which is "patient-specific" and which therefore matches the individual's unique genetic profile, in addition to being free of any risk of immune rejection.

The next step now is to create an animal model of Type I diabetes in which the new cells can be studied. Eventually, the ultimate goal is to develop a clinical therapy from the procedure which can be used in human patients to replace the pancreatic beta islet cells that are destroyed by Type I diabetes.

According to Susan Solomon, J.D., CEO of the New York Stem Cell Foundation, which cofunded the study, "This is a big deal. Tackling the basic biology of Type 1 diabetes, which is a very complex disease, is a critical step. With these cells, we can see in a dish what's happening to the immune system, and if you don't understand the immune response, you get nowhere with Type 1 diabetes." As Dr. Meri Firpo of the Stem Cell Institute at the University of Minnesota further adds, "This is very preliminary data, but now we could potentially look at the interaction between immune system cells and insulin-producing cells to find the root cause or trigger, which we think might vary from patient to patient."

Meanwhile, however, such a therapy is still in the developmental stage, and the new insulin-producing cells are currently disqualified from clinical use since the genetic manipulation that is used for reprogramming the cells poses too many medical risks. Among other problems, cells from mice that have been reprogrammed according to this method have been found to develop into teratomas (tumors) when the cells were readministered to the mice. According to Julia Greenstein of the Juvenile Diabetes Research Foundation (JDRF), the most immediate applications of Dr. Melton's new achievement "are primarily research-related". As she further explains, "Our hope is that understanding all of these things will come together - that once we've figured out how to make the cell source, we will have also figured out how to block the immune response, but there's a lot of basic science one has to do to get there." Nevertheless, "There's an incredible amount of exciting research that has the capacity to impact the disease in the long-term," she adds.

Believed to be of autoimmune origin, Type I diabetes destroys the insulin-producing beta islet cells of the pancreas. Though not as common as Type II diabetes, Type I diabetes is currently untreatable by conventional medical therapies, which offer no known cure for the disease. Since there is a strong genetic susceptibility, researchers believe that "patient-specific" therapies which are derived from each patient's own unique cells should offer the most efficacious type of treatment. Such therapies would also eliminate any need for dangerous immunosuppressive drugs - if or when such therapies are ever actually developed from iPS cells, some day, at some undetermined point in the future.

Of course, "patient-specific" therapies already exist, today, and have already been derived from autologous adult stem cells and are already being used in clinics around the world for a wide variety of diseases and injuries, without any risk of immune rejection and without any need for dangerous immunosuppression - should anyone be interested to notice.



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