Salk scientists produce functional, insulin-producing cells

Scientsts have solved a longstanding problem in the effort to create functional insulin-producing cells for diabetic patients.

The result is the production of hundreds of millions of lab-produced human beta cells–able to relieve diabetes in mice.

For more than a decade, scientists across the globe strived to replace failing pancreatic beta cells linked to immune destruction in children (type 1 diabetes) or obesity-associated diabetes in adults (type 2 diabetes). Although cells made in a dish were able to produce insulin, they were sluggish or simply unable to respond to glucose.

“We found the missing energy switch needed to produce robust and functional human beta cells, potentially turning this discovery into a viable treatment for human diabetes,” says Ronald Evans, director of the Gene Expression Laboratory at the Salk Institute.

The Salk technology begins with induced pluripotent cells (iPSC), a stem cell technique where tissue from a patient is reprogrammed into other types of cells, such as from the pancreas. This step yields the pre-beta cells, which produce insulin but are not yet functional. While several research groups reached this juncture, the road forward to functional cells was not clear.

“Pancreatic beta cells must be able to do two things to work effectively: respond to glucose and produce insulin,” says Evans. “No one had been able to figure out how to make pancreatic cells from human patients that can do both until now.”

ERR-gamma ‘crucial’

The Salk team closely studied the basic biology of a beta cell and uncovered several molecular switches, called transcription factors, that were switched off but might control the transition to a fully functional state. The Salk team found that one particular switch, called ERR-gamma, was crucial in awakening silent beta-like cells that could now respond to glucose and release insulin accordingly.

Salk scientists found a master genetic switch (ERR-gamma) critical for prompting pancreatic cells to successfully detect and respond to sugar in the blood. This discovery allows the team to grow patient-derived, functional beta cells for transplantation in a potential new diabetes therapy. CREDIT: The Salk Institute

“This advance will result in a better controlled insulin response than currently available treatments,” says Michael Downes, a Salk senior staff scientist. “Previously there was nothing known about the maturation process in beta cells. We peeked into that black box and now we know what’s going on.” He adds that the team’s technique is an easy, fast and inexpensive way to make transplantable human pancreatic beta cells in a dish that genetically match patients.

But can these beta cells successfully treat diabetes? The Salk researchers found that, indeed, when the matured beta cells were transplanted into type 1 diabetic mice, the procedure quickly rescued their diabetes. “Hopefully, this mirrors what would happen in the clinic – after someone is diagnosed with diabetes they could potentially get this treatment,” says Evans. “It’s exciting because it suggests that cells in a dish are ready to go.”

The researchers hope to move to human trials within the next few years.