Scientists have tweaked the technique for turning human stem cells into insulin-secreting beta cells and shown that the resulting cells are more responsive to fluctuating glucose levels in the blood. Stem cells can be transformed into cells that produce insulin, the hormone that controls blood sugar, according to the study published in the journal Stem Cell Reports. However, there is a major challenge: the amount of insulin produced by these cells is difficult to control.
The researchers at the Washington University in the US transplanted the beta cells into mice that could not make insulin. They found that the new cells began secreting insulin within a few days, and continued to control blood sugar in the animals for months.
"We have been able to overcome a major weakness in the way these cells previously had been developed. The new insulin-producing cells react more quickly and appropriately when they encounter glucose," said Jeffrey R Millman, an assistant professor at the Washington University. "The cells behave much more like beta cells in people who do not have diabetes," Millman said.
The researchers now believe it may be time to evaluate whether the same stem-cell approach could produce insulin and effectively control blood sugar in people. "Previously, the beta cells we manufactured could secrete insulin in response to glucose, but they were more like fire hydrants, either making a lot of insulin or none at all," Millman said. "The new cells are more sensitive and secrete insulin that better corresponds to the glucose levels," he said.
Millman's laboratory grew beta cells from human stem cells, but they made numerous changes to the "recipe" for producing insulin-producing beta cells. The researchers treated the cells with different factors at different times as they grew and developed to help the cells mature and function more effectively.
After that process was complete, the researchers transplanted the beta cells into diabetic mice with suppressed immune systems so that they would not reject the human cells. Those transplanted cells produced insulin at levels that effectively controlled blood sugar in the mice, functionally curing their diabetes for several months, which, for most of the mice in the study, was about the length of their lives.
Millman said he cannot predict exactly when such cells may be ready for human trials but believes there are at least two ways that stem cell-derived beta cells could be tested in human patients. "The first would be to encapsulate the cells in something like a gel -- with pores small enough to prevent immune cells from getting in but large enough to allow insulin to get out," he said.
"Another idea would be to use gene-editing tools to alter the genes of beta cells in ways that would allow them to 'hide' from the immune system after implantation," Millman said. He added if stem cell-derived beta cells are proven safe and effective for people with diabetes, the method of manufacturing the cells quickly could be ramped up to an industrial scale.