Manchester and Sheffield: Turning embryonic stem cells into pancreatic islets

Research lead

Scientists at Manchester and Sheffield universities in the UK have discovered a new technique for turning embryonic stem cells into insulin-producing pancreatic tissue, or islets, for the treatment of Type I diabetes.

The researchers genetically manipulated the stem cells so that they generated a transcription factor called PAX4, which is responsible for driving the cells to differentiate into islet cells.

Controlling the differentiation of stem cells is one of the major stumbling blocks to using them as the basis of cell therapies.

“Unprompted, the majority of stem cells turn into simple nerve cells called neurons,” notes Karen Cosgrove, who led the team in Manchester’s Faculty of Life Sciences. “Less than one per cent of embryonic stem cells would normally become insulin-producing pancreatic cells, so the challenge has been to find a way of producing much greater quantities of these cells.”

The team found that the transcription factor PAX4 encouraged about 20 per cent of embryonic stem cells to become pancreatic beta cells with the potential to produce insulin when transplanted into the body.

The scientists were also able to separate the new beta cells from other types of cell produced using fluorescent-activated cell sorting, a technique that uses a special dye to colour the pancreatic cells green.

Transplanting a mixture of differentiated cells and stem cells is known to cause cancer, so the ability to isolate the pancreatic cells in the lab is a major boost to attempts to develop a successful therapy.

“Scientists have had some success increasing the number of pancreatic cells produced by altering the environment in which the stem cells develop, so the next stage of our research will be to combine both methods to see what proportions we can achieve,” said Cosgrove.

There is clinical proof of principle for using beta cell transplants to treat Type I diabetes. But transplants to date have relied on cells from cadavers. While it may be some time before this research translates through to the clinic a more immediate benefit is to provide a ready-made supply of human pancreatic for use in research and drug discovery.