Pancreatic type beta cells produced from stem cells can sense glucose, release insulin and treat a mouse model of diabetes. Christopher Intagliata reports.
One of the great promises of stem-cell biology is to use a patient’s own cells as a template to build a real, working organ or tissue in the lab. One prime example: a treatment for diabetes by turning stem cells into working pancreatic beta cells, which release insulin.
"The existing beta cells that our lab and others had created were 90 percent of the way there. But 90 percent still means not functional." Ron Evans, a molecular biologist at the Salk Institute.
Evans compares the stem-cell-derived beta cells they first made to a darkened room. "If you walk into that room, there may be everything in it that you need to be a complete room, with furniture and chairs and everything else. But it's dark. And the key is: what do you need to turn on the light?"
That light switch, Evans discovered, is a gene—called estrogen-related receptor gamma. Flip it on, and it activates a genetic circuit that ramps up mitochondria production, powers up the cell, and endows the almost-functional beta cells with the ability to sense glucose and release insulin in response.
Evans's team recently used that trick to transform stem cells into beta cells that worked just like they would in a healthy pancreas. When they transplanted those cells into mice with a mouse version of diabetes, blood glucose fell to normal levels in half the rodents. The results are in the journal Cell Metabolism. [Eiji Yoshihara et al, ERRγ Is Required for the Metabolic Maturation of Therapeutically Functional Glucose-Responsive β Cells]
Next, Evans says he'll replicate the test in diabetic primates. "Primates get diabetes in a fashion that's very similar to people. So if it works in a primate, very high probability that it's going to work in people." If it does, we might someday replace a shot of insulin with a shot of cells.
[The above text is a transcript of this podcast.]