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Islet Transplantation: Progress to Date
Recent data has shed new light on the effectiveness of islet transplantation in treating type 1 diabetes. Scientists evaluating the procedure's long-term success found that most people will achieve insulin independence for some period of time, often for several years. Some transplant centers are seeing a rate of long-term insulin independence of more than 50% using specific new treatment approaches. The data also indicate that the procedure has a beneficial long-term impact on hypoglycemia unawareness, the dangerous condition in which people with type 1 diabetes have low blood sugar but do not have the physical symptoms that normally go along with it. These findings are important because they show that islet transplantation, which is now limited to people with unstable type 1 diabetes, has the potential to become a treatment option for a wider group of people.
Current Transplant Drugs May Hinder Beta Cell Regeneration
Drugs commonly used to prevent rejection after islet transplant surgery may be inhibiting the natural regeneration of beta cells, JDRF researchers in Israel and Boston have found. The discovery suggests that using different drugs might increase the success of islet replacement by increasing the survival and growth of transplanted insulin-producing cells. The approach might also allow patients to regenerate their own beta cells.
The finding, in mouse experiments, highlights the importance of understanding the effects that immune-based therapies have on insulin-producing cells, both after islet transplants and while blocking the immune attack that causes type 1 diabetes.
Researchers using mice can now study these effects very quickly. This should help to guide the development of new treatments that block the autoimmune attack in type 1 diabetes.
The study also had some important implications for research on regeneration, which focuses on regrowing the beta cells killed by the autoimmune attack. Based on the results, scientists now believe that they may be able to promote regeneration by activating the pathways blocked by the two drugs commonly used in transplants (sirolimus and tacrolimus). The study also revealed that in mice, pancreatic beta cells can spontaneously regenerate under the right conditions - enough to allow a full recovery from diabetes. Many scientists have thought that long periods of high blood sugar affected insulin-producing cells and made regeneration impossible. But the new research shows this isn't true and adds to the evidence that people with longstanding diabetes, not just the newly diagnosed, might be able to benefit from regeneration.
Bone Marrow-Derived Mesenchymal Stem Cells Show Potential to Become Beta Cells
Dr. Shimon Efrat and his team at Tel Aviv University were able to turn bone marrow-derived mesenchymal stem cells into insulin-producing beta cells. Using an approach that involved the Pdx1 gene in combination with tissue culture conditions, the scientists developed a procedure for expanding the mesenchymal stem cells in the laboratory and differentiating them into beta cells.
These findings mean that bone marrow-derived mesenchymal stem cells have the potential to solve the "supply" problem in islet transplantation - a development that would make the treatment more widely available. Mesenchymal stem cells would offer several advantages as a cell source. First, they are relatively easy to obtain from patients. Second, if they were taken from a patient with type 1 diabetes, modified in tissue culture and then returned to the patient, scientists might be able to circumvent one of the most vexing problems in islet transplantation: the immune system attack that occurs when "foreign" tissue is introduced into the body. Because of this, people who undergo the procedure must take powerful and potentially harmful drugs to suppress their immune systems. However, if it were possible to use beta cells derived from mesenchymal stem cells, patients would be free from having to take these drugs because the body would recognize the cells as "self" instead of "foreign."
Embryonic Stem Cells Made Into Glucose-Responsive, Insulin-Secreting Cells
Scientists at the biotechnology company Novocell successfully transformed human embryonic stem cells into a primitive cell line that, when implanted into mice, was able to reverse chemically induced diabetes. JDRF partly funded the development of the stem cell lines used in this research.
The primitive cells, called pancreatic endoderm, began producing human insulin in the mice after one to three months. The cells were also shown to produce blood levels of C-peptide comparable to those seen in mice transplanted with about 3,000 isolated human islets; they also protected the mice from hyperglycemia.
The study demonstrates that under the right conditions inside the body, human embryonic stem cells can be differentiated down the path to eventually becoming insulin-secreting beta cells. This advance is important not only because of its potential to accelerate progress in understanding the development of insulin-producing beta cells, but also for the field of beta cell replacement.
