Diabetes

Is a cure for type 1 diabetes 'within reach'?

"Type 1 diabetes cure within reach after breakthrough," The Independent reports after researchers have managed to "coax" human stem cells into becoming insulin-producing cells.

Type 1 diabetes is an autoimmune condition where the body's own immune system destroys the insulin-producing cells of the pancreas. Insulin is a hormone that plays a vital role in regulating blood glucose levels.

There is currently no "cure" for type 1 diabetes and no way to replace these destroyed cells, making the person reliant on lifelong insulin injections.

This study aimed to see if it would be possible to develop these insulin-producing cells from stem cells in the laboratory. 

The researchers demonstrated they were able to successfully produce large numbers of functioning stem cell-derived cells that looked structurally similar to normal pancreatic cells, and produced insulin in response to glucose in the same way.

The function of these cells was demonstrated both in the laboratory and when transplanted into live mice, including mice genetically engineered to have diabetes.

The findings are positive, but the research is still in the very early stages. Further development will be needed to see whether stem cell-derived pancreatic cells could function normally in people with type 1 diabetes.

There is also the question as to whether the transplanted cells could also be targeted by the body's immune system.

Overall, it is too early to know whether there could one day be a complete "cure" for type 1 diabetes.

Where did the story come from?

The study was carried out by researchers from Harvard University and was funded by the Harvard Stem Cell Institute, the National Institute of Health, Helmsley Charitable Trust, the JPB Foundation and personal contributions.

It was published in the peer-reviewed scientific journal, Cell.

The UK media's reporting of the study was accurate, but talks of a "cure" for type 1 diabetes are premature.

As the authors of the study acknowledge themselves, "Much work remains to be done to achieve any of these therapeutic, disease-modelling, drug discovery or tissue engineering goals."

What kind of research was this?

This was a laboratory study that aimed to develop a generation of insulin-producing pancreatic beta cells from stem cells. 

Type 1 diabetes is an autoimmune condition where the body's own immune system for some reason destroys beta cells, making the person reliant on lifelong insulin injections. There is currently no "cure" for type 1 diabetes and no way to replace these destroyed cells.

As the researchers say, the discovery of human pluripotent stem cells (hPSC) offers a great deal of potential for medical innovation. This is because hPSCs can be converted into other specialist cell types, such as insulin-producing cells.

This then opens up the possibility of generating replacement cells and tissues in the laboratory, which could be used for disease treatment.

This study examines whether hPSCs in the laboratory could be instructed (via manipulation of signalling pathways) to develop into functioning pancreatic beta cells.

What did the research involve?

The researchers first cultured different pluripotent stem cell lines and trialled various different laboratory approaches. This was so they could make these differentiate into functioning cells that had the genetic characteristics of pancreatic beta cells.

The stem cell-derived pancreatic beta cells were then incubated in glucose solution to see if this stimulated them to produce insulin. A sequence of further glucose challenges (tests that see how the cells respond to glucose) at increasing concentrations then followed.

The researchers then compared these results with those of normal adult beta cells.

They got further confirmation of the cells' functioning by looking at changes in calcium levels within the cells, as beta cells sense changing glucose levels through calcium signalling. This helps them regulate blood glucose levels as required.

The structure of the stem cell-derived pancreatic cells was then more closely analysed in the laboratory.

As the next stage of the experiment, the stem cell-derived pancreatic cells were then transplanted into live mice with a suppressed immune system.

Two weeks after transplantation, these mice then had various glucose challenges, with blood samples taken to check their blood glucose and insulin levels. This was again compared with transplantation of normal adult beta cells.

Finally, they looked at the effects of transplanting these cells into genetically engineered "diabetic" mice.

What were the basic results?

Overall, 75% of the stem cell-derived pancreatic beta cells responded to high glucose challenges, which was similar to that for normal adult beta cells.

The amount of insulin secreted in response to glucose per stem cell-derived cell was also similar to that of normal beta cells. The cellular calcium response to glucose was also similar between the stem cell-derived cells and the normal cells.

The researchers further demonstrated that the structure and protein expression of the stem cell-derived cells was similar to the normal pancreatic cells.

When the stem cell-derived pancreatic cells were transplanted into the mice, the mice successfully secreted insulin into the bloodstream within two weeks.

In the glucose challenge, 73% of the mice with these transplanted cells (27 of 37 animals) showed increased blood insulin levels. This was in comparison to 75% (9 of 12) of those transplanted with normal pancreatic cells.

As a final stage, when transplanted into "diabetic" mice, the stem cell-derived pancreatic cells helped stop the rapidly worsening increasing blood sugar normally observed in these animals. By four months after transplantation, only one out of six of these diabetic mice had died.

How did the researchers interpret the results?

The researchers concluded that functional pancreatic beta cells can be generated from human pluripotent stem cells in the laboratory.

The results demonstrate that they function similarly to normal adult beta cells, both in the laboratory and in the live mouse model.

Conclusion

This is promising early-stage research into the possible generation of insulin-producing pancreatic beta cells from stem cells in a laboratory.

The researchers demonstrated that they were able to successfully produce large numbers of functioning stem cell-derived cells that looked structurally similar to normal beta cells and produced insulin in response to glucose in the same way.

The successful function of these cells was demonstrated both in the laboratory and when transplanted into mice, including mice genetically engineered to have diabetes.

There is currently no "cure" for type 1 diabetes and no way to replace these destroyed cells. This stem cell research, which holds promise for a possible generation of replacement pancreatic cells, is therefore encouraging.

However, research is still in the very early stages, with studies only having been carried out on a small number of live mice.

Much further development is needed to see whether it could be possible to perform human trials to see whether stem cell-derived pancreatic cells could function normally in people with type 1 diabetes.

Various questions still need to be answered, including whether the transplanted cells could also be targeted by the body's immune system.

Overall, the research is promising, but it is too early to know whether there could one day be a complete "cure" for type 1 diabetes.


NHS Attribution