Type 1 Diabetes Treatment Gets Boost from Stem Cells

TIME Health medicine Type 1 Diabetes Treatment Gets Boost from Stem Cells Insulin-making cells grown from stem cells glow green two weeks after they are transplanted into mice (c) Douglas Melton 2014 Scientists started with stem cells and created the first insulin-making cells that respond to changes in glucose

Scientists are closer to a potential stem cell treatment for type 1 diabetes.

In a new article in the journal Cell, Douglas Melton, co-director of the Harvard Stem Cell Institute (and one of the 2009 TIME 100) and his colleagues describe how they made the first set of pancreatic cells that can sense and respond to changing levels of sugar in the blood and churn out the proper amounts of insulin.

Its a critical first step toward a more permanent therapy for type 1 diabetics, who currently have to rely on insulin pumps that infuse insulin when needed or repeated injections of the hormone in order to keep their blood sugar levels under control. Because these patients have pancreatic beta cells that dont make enough insulin, they need outside sources of the hormone to break down the sugars they eat.

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Melton started with two types of stem cells: those that come from excess embryos from IVF procedures, and those that can be made from skin or other cells of adults. The latter cells, known as iPS cells, have to be manipulated to erase their developmental history and returned back to an embryonic state. They then can turn into any cell in the body, including the pancreatic beta cells that produce insulin. While the embryonic stem cells from IVF dont require this step, they arent genetically matched to patients, so any beta cells made from them may cause immune reactions when they are transplanted into diabetic patients.

Both techniques, however, produced similar amounts of insulin-making beta cellssomething that would have surprised Melton a few years ago. But advances in stem cell technology have made even the iPS cells pretty amenable to reprogramming into beta cells. Meltons group tested more than 150 different combinations of more than 70 different compounds, including growth factors, hormones and other signaling proteins that direct cells to develop into specific cell types, and narrowed the field down to 11 factors that efficiently turned the stem cells into functioning beta cells.

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The two populations of stem cells churned out hundreds of millions of insulin-making cells, which is the volume of cells that a patient with type 1 diabetes would need to cure them and free them from their dependence on insulin. An average patient, says Melton, would need one or two large coffee cups worth of cells, each containing about 300 million cells. Melton and his team then conducted a series of tests in a lab dish to confirm that the cells were functioning just like normal beta cells by producing more insulin when they were doused with glucose, and less when glucose levels dropped. That was a huge advance over previous efforts to make beta cells from stem cellsthose cells could produce insulin, but they didnt respond to changing levels of glucose and continuously pumped out insulin at will.

Next, the scientists transplanted about five million of the stem cell derived beta cells into healthy mice, and two weeks later, gave them an injection of glucose. About 73% of the mice produced enough insulin to successfully break down the sugar. Whats more, that was similar to the proportion of mice responding to glucose after getting a transplant of beta cells from human cadavers. That was especially encouraging since some type 1 diabetics currently receive such transplants to keep their diabetes under control. Weve now shown that we can produce an inexhaustible source of beta cells without having to do to cadavers, he says.

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Type 1 Diabetes Treatment Gets Boost from Stem Cells