Turning stem cells into insulin-producing cells

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Type 1 diabetes is a chronic condition in which the pancreas produces little or no insulin due to the immune system attacking the cells. In a small number of cases, diabetics can have a pancreas transplant but there is limited availability.

Transplants of just the pancreatic ‘islets’ – clusters of cells containing healthy beta cells – are currently in clinical trials, but still rely on pancreases from deceased donors.

Dr Matthias Hebrok, senior author of the study at University of California San Francisco (UCSF), said: ‘The cells we and others were producing were getting stuck at an immature stage where they weren’t able to respond adequately to blood glucose and secrete insulin properly.
‘It has been a major bottleneck for the field. ‘The team, led by Dr Gopika Nair, instead looked at the physical process by which the cells separate from the rest of the pancreas and form the so-called islets of Langerhans.

It was the formation of this islet that appeared to be important, rather than the individual cells themselves.
Dr Nair said: ‘A key principle in biology is that form follows function, so we reasoned that the formation of islets might be an important process for beta cells to mature properly.’ The researchers replicated the process in lab dishes by artificially separating partially differentiated pancreatic stem cells.
They then reformed them into islet-like clusters and the cells’ development suddenly leapt forward.

The researchers then transplanted these lab-grown ‘islets’ into healthy mice and found that they were functional in three days and produced insulin in response to blood sugar. Dr Hebrok said: ‘We can now generate insulin-producing cells that look and act a lot like the pancreatic beta cells you and I have in our bodies. ‘This is a critical step towards our goal of creating cells that could be transplanted into patients with diabetes.’

Current therapeutics like insulin injections only treat the symptoms of the disease. The work points to several exciting avenues to finally finding a cure.’
Diabetics can manage their disease, but are at risk of serious health complications including kidney failure, heart disease and stroke. Patients may be eligible for a pancreas transplant from a deceased donor if they also have severe kidney disease, or if they have severe episodes of a dangerously low blood sugar level (hypoglycaemia) that occur without warning, in spite of good insulin control. The procedure is risky, and recipients must take immune-suppressing drugs for life, which can put them at greater risk of infection.
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