imaging mass cytometry

Rescuing beta cells could slow down or even stop the progress of type 1 diabetes

by Barbara Hewitt on February 4, 2019

Scientists are looking at how type 1 diabetes gradually destroys insulin production in the body and if beta cells could be rescued or the destruction slowed down.

Using new Imaging Mass Cytometry, the researchers at the University of Zurich looked at beta cells in the pancreas of healthy organ donors and those with type 1 diabetes.

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They found that many beta cells, which normally produce insulin, are still present in the early stages of the disease, but look very different. They believe that these beta cells could potentially be rescued for the benefit of the patient and the progression of the disease could be slowed down or even stopped.

The pancreatic islets of Langerhans play a key role when it comes to regulating how the body metabolizes sugar. They monitor blood sugar levels and secrete insulin as required. Insulin in turn triggers the uptake of sugar into cells. In patients suffering from type 1 diabetes, these cells are attacked and destroyed by the body’s own white blood cells.

Little is known about what happens inside of the pancreas when diabetes develops, since performing biopsies or high resolution imaging of the organ is not feasible when patients are alive.

‘Much of what we know about type 1 diabetes in humans is based on pancreases from organ donors, and these are very rare,’ said Bernd Bodenmiller from the Institute of Quantitative Biomedicine of the University of Zurich. This is why researchers are keen to gain as many insights as possible from every single organ that is donated.

Bodenmiller and his team, working together with research groups in Geneva and in the United States, have now for the first time used imaging mass cytometry to investigate donated pancreases.

‘This allows us to visualize beta cells, other types of cells in the Langerhans islets as well as invading immune cells at the same time. This has previously not been possible using traditional approaches,’ explained Bodenmiller.

Nicolas Damond, first author of the study from the Institute of Quantitative Biomedicine, analysed 12 donated pancreases of which four were from healthy donors, four from patients in the early stages of type 1 diabetes and four from patients with advanced type 1 diabetes. The scientists used the findings to develop a map that shows the location of the different cell types in the pancreatic islets and the state the beta cells were in.

Damond then compiled the data from the various donated organs in a pseudo timeline. This allowed him to reconstruct the changes in the pancreatic tissue from the onset of type 1 diabetes right up to the final stages of the disease.

One of the findings was particularly interesting for the researchers and that was that there was still a surprisingly high number of beta cells in the pancreatic islets of Langerhans during the disease’s early stages. These cells might look different and produce less insulin than healthy cells, but they could possibly still be saved from complete destruction.

‘If we succeed in stopping the autoimmune attack this early, the cells could maybe regain their function and help with regulating the blood sugar levels of patients,’ said Damond.

Through imaging mass cytometry the research group also located the special type of white blood cells which, according to current scientific knowledge, are responsible for beta cell destruction. The researchers found these immune cells mainly in the pancreases of patients in early stages of the disease, especially in pancreatic islets that contained a high number of surviving beta cells. Pancreatic islets whose beta cells had been mostly destroyed, in contrast, had fewer white blood cells.

These results could help to shed light on the mechanism of the autoimmune reaction, about which there are currently still many open questions. ‘Our study demonstrates that imaging mass cytometry can make a valuable contribution to a better understanding of how type 1 diabetes progresses. It provides a basis for planning further experiments and developing new hypotheses,’ Bodenmiller added.

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