Beta cell boost could replace insulin injections

A strategy for deriving beta cells from patients with type I diabetes could transform disease treatment.

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2016, Jeffrey Millman

Disease-specific stem cells show great promise because they can be used for cell replacement therapies, drug screening and investigating disease progression. Now, scientists from the US have developed viable beta cells (β cells), which are responsible for generating insulin in the body, using stem cells derived from patients with type I diabetes (T1D). Their results may mean that diabetic patients could receive personalized β cell boosts instead of having to inject insulin.  

β cells, located in the pancreas, make, store and release insulin in response to peaks in blood sugar levels. T1D is caused by the autoimmune-fuelled destruction of these cells. Since β cells are the main targets in T1D progression, stem cell therapy aimed at replenishing them could prove invaluable.  

“In 2014, we developed a strategy for generating functional β cells from human pluripotent stem cells,” says Jeffrey Millman at Washington University School of Medicine, who led the project. “Now, we have extended this approach to generate β cells from stem cells derived from T1D patients.  We have never had access to β cells from T1D before because they are so quickly damaged or destroyed during disease progression.” 

The researchers began by deriving immature pluripotent stem cells from skin samples taken from T1D patient volunteers. Pluripotent stem cells are reprogrammed adult cells that have the ability to turn into other kinds of cells. Millman’s team then used chemicals and proteins to manipulate the necessary signalling pathways and mimic the signals necessary to trigger differentiation into β cells.  

“The technology required for this to work has only become available in the last two years. Before then, performing this project was literally science fiction,” says Millman. “We had no idea whether the T1D-derived β cells would even be viable.” 

The team tested their T1D β cells in cultures and in diabetic mice to see how the cells would respond to glucose injections. They found that the β cells were fully functional and secreted insulin when they sensed glucose levels rising. There was no discernable difference between them and β cells from healthy individuals.  

There are two key benefits of this technology.  Firstly, these cells could be transplanted into patients, meaning they wouldn’t need insulin injections and their blood glucose control would improve considerably. Since these cells can be derived from the patient, there would be no immune rejection of the transplanted cells when combined with a therapy to suppress autoimmunity, Millman adds.  

Secondly, this presents an opportunity to study T1D β cells for the first time. “New insights into diabetes initiation could be uncovered that may one day lead to a preventative therapy,” says Millman.

References

  1. Millman, J.R., Xie, C., Van Dervort, A., Gürtler, M., Pagliuca, F.W. & Melton, D.A. Generation of stem cell-derived β-cells from patients with type 1 diabetes. Nature Communications 7, 11463 (2016). | article

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