The researchers converted human stem cells into insulin-producing cells and demonstrated in mice infused with these cells that blood sugar levels can be controlled and diabetes functionally cured for nine months.
The findings, from researchers at the Washington University School of Medicine in St. Louis, were published online February 24 in the journal Nature Biotechnology.
“These mice had very severe diabetes with blood sugar readings of over 500 milligrams per deciliter of blood – levels that could be fatal to a person – and when we gave the mice insulin-secreting cells, within two weeks their levels of Blood glucose had returned to normal and remained so for many months, “said lead researcher Jeffrey R. Millman, assistant professor of medicine at the School of Medicine and biomedical engineering at the McKelvey School of Engineering.
Several years ago, the same researchers discovered how to convert human stem cells into pancreatic beta cells that produce insulin. When these cells meet blood sugar, they secrete insulin. However, previous work had its limitations and did not effectively control diabetes in mice.
Now, researchers have shown that a new developed technique can more efficiently convert human stem cells into insulin-producing cells that control blood sugar more effectively.
“A common problem when you’re trying to turn a human stem cell into an insulin-producing beta cell – either a neuron or a heart cell – is that you also produce other cells you don’t want,” said Millman. “In the case of beta cells, we could get other types of pancreatic or liver cells.”
The pancreas and off-target liver cells don’t hurt anything when implanted in a mouse, but they don’t fight diabetes either.
“The more off-target cells you get, the less therapeutically relevant cells you have,” he said. “You need about a billion beta cells to treat a person with diabetes. But if a quarter of the cells you make are actually liver cells or other pancreas cells, instead of needing a billion cells, you will need 1.25 billion cells. It makes it 25% harder to cure the disease. “
Using the new technique, Millman’s team found that far fewer off-target cells had been produced while the beta cells that had been produced had improved function. The technique is aimed at the internal cell scaffolding, called the cytoskeleton. The cytoskeleton is what gives a cell its shape and allows the cell to interact with its surroundings, converting physical signals into biochemical signals.
“It’s a completely different approach, substantially different in the way we approach it,” he said. “Previously, we would have identified various proteins and factors and scattered them over the cells to see what would happen. Since we understood the signals better, we managed to make this process less random.”
Understanding this process allowed the Millman team to produce more beta cells. It is important to note that the new technique works efficiently on stem cells from multiple sources, greatly expanding the ability of this technique in studying the disease.
“We were able to produce more beta cells and those cells worked better in mice, some of which have been treated for more than a year,” said Millman.
He explained that there is still much to be done before this strategy can be used to treat people with diabetes. They will have to test cells for longer periods in larger animal models and work to automate the process so that they have every hope of producing beta cells that will help the millions of people who currently require insulin injections to control their diabetes. But the search continues.