A cure for type 1 diabetes has long eluded even the top experts; not because they do not know what must be done, but because the tools did not exist to do it.

However, scientists at the Gladstone Institutes, harnessing the power of regenerative medicine, have now developed a technique in animal models that could replenish the very cells destroyed by the disease. The team’s findings, published online in the journal Cell Stem Cell, are an important step towards freeing an entire generation of patients from the life-long injections that characterise this disease.

Type 1 diabetes, which usually manifests during childhood, is caused by the destruction of ß-cells, a type of cell that normally resides in the pancreas and produces a hormone called insulin. Without insulin, the body’s organs have difficulty absorbing sugars, such as glucose, from the blood.

Once a death sentence, the disease can now be managed with regular glucose monitoring and insulin injections. A more permanent solution, however, would be to replace the missing ß-cells. But these cells are hard to come by, so researchers have looked towards stem cell technology as a way in which to make them.

‘The power of regenerative medicine is that it can potentially provide an unlimited source of functional, insulin-producing ß-cells that can then be transplanted into the patient,’ said Dr Ding, who is a professor at the University of California, San Francisco (UCSF), with which Gladstone is affiliated.

‘Previous attempts to produce large quantities of healthy ß-cells — and to develop a workable delivery system — have not been entirely successful. So we took a somewhat different approach.’

One of the major challenges to generating large quantities of ß-cells is that these cells have limited regenerative ability; once they mature it is difficult to make more. So the team decided to go one step backwards in the life cycle of the cell.

The team first collected fibroblasts from laboratory mice. Then, by treating the fibroblasts with a unique ‘cocktail’ of molecules and reprogramming factors, they transformed the cells into endoderm-like cells. Endoderm cells are a type of cell found in the early embryo, and which eventually mature into the body’s major organs (including the pancreas).

‘Using another chemical cocktail, we then transformed these endoderm-like cells into cells that mimicked early pancreas-like cells, which we called PPLCs,’ said Gladstone Postdoctoral Scholar Ke Li, the article’s lead author.

‘Our initial goal was to see whether we could coax these PPLCs to mature into cells that, like ß-cells, respond to the correct chemical signals and — most importantly — secrete insulin. And our initial experiments, performed in a petri dish, revealed that they did.’

The research team then wanted to see whether the same would occur in live animal models. So they transplanted PPLCs into mice modified to have hyperglycaemia (high glucose levels), a key indicator of diabetes.

‘Importantly, just 1 week post-transplant, the animals’ glucose levels started to decrease gradually approaching normal levels,’ said Dr Li. ‘And when we removed the transplanted cells, we saw an immediate glucose spike, revealing a direct link between the transplantation of the PPLCs and reduced hyperglycaemia.’

However, it was when the team tested the mice 8 weeks post-transplant that they saw more dramatic changes: the PPLCs had given rise to fully functional, insulin-secreting ß-cells.

‘These results not only highlight the power of small molecules in cellular reprogramming, they are proof-of-principle that could one day be used as a personalised therapeutic approach in patients,’ explained Dr Ding.