Making beta cells from people with type 1 diabetes

Making beta cells from people with type 1 diabetes

Research Update Dec. 27, 2016

Scientists generated functional β (beta) cells from the skin cells of people with type 1 diabetes. In type 1 diabetes, a misguided attack by the immune system leads to destruction of insulin-producing β cells found in clusters called islets in the pancreas. Although administration of insulin via injections or a pump is life-saving, it does not mimic the exquisite blood glucose (sugar) control of the pancreas. Therefore, scientists are pursuing strategies to replace the destroyed β cells. One way to do that is through islet transplantation—an experimental procedure using islets from a cadaveric donor. The procedure has shown promise for people with difficult-to-control diabetes, but has significant challenges: donor islet tissue is limited, and immunosuppressive medications, which have toxic side effects, are required to prevent rejection of tissue transplanted from another individual. Toward overcoming the first barrier, scientists recently developed a new laboratory production method to make large quantities of β cells—called stem-cell derived β (SC-β) cells—from human stem cells. This method could, with further development, be used to make β cells from a sample of cells from a person with type 1 diabetes in the quantities needed for transplantation back into that same person. These cells would likely require protection from the autoimmune attack, but might not require toxic immunosuppressive medications to prevent rejection of the tissue. To investigate this possibility, in new research, scientists used skin cells from three people with type 1 diabetes (T1D cells) and three people without diabetes (ND cells). By introducing specific factors into these cells and using the new large-scale production method they developed, they made the skin cells become stem cells—cells that could subsequently become any cell type. They then, by introducing other factors, coaxed these stem cells to become SC-β cells (T1D SC-β cells and ND SC-β cells). Cells from the two different origins showed no differences in the ability to become SC-β cells, indicating for the first time that cells from a person with type 1 diabetes could be used to make SC-β cells. Next, the scientists demonstrated that the T1D SC-β cells functioned like healthy β cells. For example, in laboratory culture, T1D SC-β cells secreted insulin in response to glucose; they also released insulin in response to diabetes drugs that are known to stimulate insulin secretion, demonstrating their potential for use in screening for new diabetes drugs. The T1D SC-β also functioned in live animals: when T1D SC-β cells were transplanted into male mice, they produced insulin in response to glucose and controlled the animals’ blood glucose levels. Many research questions remain before an SC-β cell transplant procedure will be ready for testing in humans. First, it remains possible that differences between T1D SC-β and ND SC-β cells could appear over a longer time period than in the study. Second, it is not known how the T1D SC-β cells will interact with the recipient’s immune system; for example, it is not yet clear whether these cells could still be rejected, even though they were derived from the recipient’s own cells; and it is likely that these cells would be subject to the same autoimmune attack that destroyed the person’s original β cells. Third, individual differences in type 1 diabetes may affect the production, function, or transplant success of T1D SC-β cells. Thus, further research will illuminate the potential of T1D SC-β cells as a therapy for type 1 diabetes. Nonetheless, these results mark another significant step forward toward a cell therapy for type 1 diabetes, and also provide a valuable resource for drug screening and studying the development of the disease.

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