Two new studies report the creation of functioning human beta cells, which can release insulin in response to changes in blood sugar, holding promise for the treatment of diabetes.
In the first study, published in Nature Communications, scientists extracted fat cells from a 50-year-old subject and turned these into stem cells. They then used a 'synthetic gene network' to programme the cells to become functioning beta cells that secrete insulin.
Professor Martin Fussenegger of ETH Zurich and his team first identified the specific growth factors that are involved in the normal development of stem cells into beta cells. The timing of the release of these growth factors is crucial to the process but had been hard to recreate.
Scientists had tried adding growth factors directly to cells growing in the laboratory, but this had proved tricky. 'It's not only really hard to add just the right quantities of these components at just the right time, it's also inefficient and impossible to scale up,' said Professor Fussenegger.
His team created a synthetic gene network, which they added to the stem cells, instructing the cell to produce the growth factors at exactly the right time and in precisely the right amounts. The beta cells produced in this way closely resembled normal beta cells and also contained insulin.
They hope to develop the process into an individualised treatment for diabetes using a patient's own fat cells.
In a second study, carried out at the Salk Institute in La Jolla, California, and published in Cell Metabolism, researchers solved a common problem encountered in this area. Previously, new beta cells generated in the laboratory would be 'stuck' at a certain stage of development and be unable to respond to glucose, even though they could produce insulin.
The researchers noted that healthy beta cells produce a protein called ERR-gamma in high levels. Genetically modified mice that did not produce ERR-gamma were also unable to produce insulin in response to a spike in blood glucose.
So the team, led by Professor Ronald Evans, programmed laboratory grown human beta cells, derived from induced pluripotent stem cells, to produce extra ERR-gamma. 'Those cells in culture began to respond to glucose and release insulin,' said Professor Evans.
When these beta cells were injected into mice with diabetes, they also restored normal blood glucose control.
'I believe this work transitions us to a new era in creating functional beta cells at will,' said Professor Evans. His team also hopes develop these techniques for use in human trials in the next few years.