Clustered stem cells become working insulin producers in potential cure for diabetes
Diabetes is the result of the body's inability to keep blood-sugar levels in check, something that is normally handled by insulin. More and more research is tracing this problem back to faulty beta cells in the pancreas that are failing to produce this hormone, and more and more research is uncovering potential pathways to restore their function. Medical scientists have now made a promising breakthrough in this area, describing a novel technology that converts stem cells into insulin-secreting beta cells by harnessing an often overlooked step in their maturation.
Improperly functioning beta cells in the pancreas are thought to be central to type 1 diabetes, failing to produce much-needed insulin and keep tabs on sugar levels in the blood. Sufferers tend to this problem by manually monitoring blood-sugar levels and injecting insulin as needed, but this is laborious and uncomfortable.
Another option is a pancreas transplant, but the organs aren't easy to come by. According to scientists at the University of California San Francisco (UCSF), of the 1.5 million sufferers of type-1 diabetes in the US, only around 1,000 receive a pancreas transplant each year. And those that do can still experience complications and failure, often driven by an immune response following implantation.
So developing synthetic sources of the invaluable beta cells would be a huge boon for treatment of diabetes, and there is some exciting advances happening in this area. These include an artificial pancreas that was recently approved by the FDA, synthetic versions that mimic the real deal and new technologies that can produce beta cells in large quantities.
Among the scientists leading the charge in this area is Matthias Hebrok, director of the Diabetes Center at UCSF. Hebrok and his team seek to grow meaningful amounts of healthy beta cells that can then be transplanted into patients, using stem cells as a starting point. But Hebrok, and others pursuing similar approaches have run into trouble getting the cells to mature properly. "It has been a major bottleneck for the field," he says.
Now Hebrok and his team believe they cracked the code, taking inspiration from a natural process whereby beta cells in the pancreas form clusters called the islets of Langerhans. The scientists recreated this process, manually sorting beta cells into clusters and transplanting them into healthy mice. They then watched on as the cells matured within days and began producing insulin in response to glucose levels, just as healthy cells would.
In similar but separate research at Washington University in St Louis last month, scientists made a similar breakthrough to produce mature beta cells that secreted insulin in a matter of days. They achieved this by treating the cells with various growth factors along the way. What's different about the new research out of UCSF, is that the technique seems to take other cells along for the ride.
"We are separating cells at the immature beta cell stage and recombining desired cell populations, such as cells that are positive for insulin," Hebrok explains to New Atlas. "Re-aggregation not only generates beta cells, but also other endocrine islet cell types, like alpha and delta cells. Having other islet cells present likely will be beneficial in the long run as this is closer to the normal cellular organization found in native human islets."
Producing these cells and observing their success in animal models is one thing, implanting them into human diabetes sufferers is very much another. To that end, the scientists are now working with the university's bioengineers and gene-editing experts to tweak the cells so they can be transplanted into patients without the need for drugs that suppress the immune system so they can take hold. Another possibility is the development of drugs that bolster the small amount of beta cells in diabetes sufferers as a way of kickstarting insulin production.
"We're finally able to move forward on a number of different fronts that were previously closed to us," Hebrok added. "The possibilities seem endless."
The research was published in the journal Nature Cell Biology.