A breakthrough in type-1 diabetes, which affects about 400,000 children and adults in Britain, has resulted from a study showing that it is possible to make vast quantities of insulin-producing cells for patient transplants.
Scientists have for the first time managed to make hundreds of millions of mature human pancreatic cells to treat diabetic mice successfully over long periods of time. The researchers believe that human clinical trials could begin within a few years with long-term, subcutaneous implants that would make daily insulin injections redundant.
Human stem cells were coaxed into mature “beta” cells, which make the insulin hormone within the pancreas, using a cocktail of 11 chemical growth factors. Patients with type-1 diabetes lack beta cells because they are destroyed by their own immune systems.
Scientists at Harvard University in Cambridge, Massachusetts, who carried out the study, said that it should be possible to produce “scalable” quantities of beta pancreatic cells from stem cells in industrial-sized bioreactors and then transplant them into a patient within an implant to protect them from immune attack.
This would result in an effective cure for a childhood illness that currently requires daily injections of insulin for life to control glucose levels in the blood. “A scientific breakthrough is to make functional cells that cure a diabetic mouse, but a major medical breakthrough is to be able to manufacture at large enough scale the functional cells to treat all diabetics. This research is therefore a scientific and potentially a major medical breakthrough,” said Chris Mason, professor of regenerative medicine at University College London.
“If this scalable technology is proven to work in both the clinic and in the manufacturing facility, the impact on the treatment of diabetes will be a medical game-changer on a par with antibiotics and bacterial infections,” said Professor Mason, who was not involved in the study, published in the journal Cell.
Making industrial quantities of the insulin-producing cells of the pancreas has been a holy grail of diabetes research and many previous attempts have come close, although none has achieved scalable quantities of the mature beta cells that could be of practical benefit to diabetic patients.
“There have been previous reports of other labs deriving beta cell types from stem cells, [but] no other group has produced mature beta cells as suitable for use in patients,” said Professor Doug Melton of Harvard University, who led the study in Cell.
“The biggest hurdle has been to get to glucose-sensing, insulin-secreting beta cells, and that’s what our group has done,” said Professor Melton, who was inspired to start the research 23 years ago after his infant son Sam was diagnosed with type-1 diabetes.
The researchers screened about 150 different chemicals and found 11 that in combination could be used to coax human stem cells into fully-mature beta pancreatic cells, which were found to produce reliable and meaningful quantities of insulin when transplanted into diabetic mice.
“You never know for sure that something like this is going to work until you’ve tested it numerous ways. We’ve given these cells three separate challenges with glucose in mice and they’ve responded appropriately, that was really exciting,” Professor Melton said.
“It was gratifying to know that we could do something that we always thought was possible, but many people felt it wouldn’t work. If we had shown this was not possible, then I would have had to give up on this whole approach. Now I’m really energised,” he said.
In addition to offering a new form of treatment – and possibly a “cure” – for type-1 diabetes, the researchers believe it could also offer hope for the 10 per cent of type-2 diabetics who have to rely in regular insulin injections.
Professor Melton said that the mice treated with the transplanted pancreatic cells are still produce insulin many months after being injected. Trials on laboratory monkeys are however needed before the technology can be transferred into humans.
“We are now just one pre-clinical step away from the finish line,” said Professor Melton, who also has a daughter with type-1 diabetes.
Mark Dunne, professor of physiology at Manchester University, said that Professor Melton’s team has made an important scientific advance that could fundamentally change the way diabetic patients are treated in the future.
“I think it’s a major advance. The experiments show these beta cells look as good as the human equivalent and other groups haven’t been able to show that. That’s a very important breakthrough in the field,” Professor Dunne said.
Daniel Anderson, professor of applied biology at the Massachusetts Institute of Technology, who is working with Professor Melton on an implantable device, said: “This advance opens the doors to an essentially limitless supply of tissue for diabetic patients awaiting cell therapy.”