Researchers from the Karolinska Institute, Sweden, managed to prevent Type 1 Diabetes onset in genetically susceptible mice, according to an article published in Diabetes. The scientists explain that they injected the mice with specifically prepared cells, which stopped their immune systems from destroying the pancreatic beta cells - cells that produce insulin - just in time.
Type 1 diabetes occurs when the body's immune system attacks and destroys the insulin-producing beta cells as if they were harmful pathogens - the immune system confuses them for alien bodies that cause harm. As beta cells become destroyed, insulin production goes down. Eventually, the patient has to inject insulin.
Experts are not sure what causes the immune system to attack the beta cells.
Beta cells are located in the so-called islets of Langerhans (islets), in the pancreas - they make up 65% to 80% of the cells in the islets. A healthy pancreas has about 1 million islets distributed throughout it. The islets produce and secrete at least 5 different types of hormones into the bloodstream: alpha cells produce glucagon, beta cells produce insulin and amylin, delta cells produce somatostatin, PP cells produce pancreatic polypeptide, and epsilon cells produce ghrelin.
Light microscopy - a mouse pancreatic islet. The beta cells are in green (insulin staining), glucagon in red, and the nuclei in blue
Scientists do know, however, that certain immune cells, macrophages, are highly active and play a major role in beta cell destruction in Type 1 diabetes. On the other hand, macrophages can do the opposite - studies have shown that they can protect against inflammation-mediated tissue damage.
Immune cells communicate with each other by using cytokines - signal molecules. They tell each other what to do.
Robert Harris and team set out to find out which cytokines were involved in instructing the macrophages to become protectors, rather than destroyers.
Robert Harris said:
"We managed to achieve this aim, defining a novel combination of cytokines that confer on macrophages the ability to protect mice from developing Type 1 diabetes.
It has never previously been reported, that such an adoptive transfer cell therapy can be used in Type 1 diabetes and this study could thus represent a major advance towards disease prevention"
The scientists used non-obese diabetic (NOD) mice - these animals are generally susceptible to becoming Type 1 diabetics within 12 to 30 weeks after birth. The authors grew macrophages from bone marrow progenitors within the mice. They then stimulated the mature macrophage with a specific set of cytokines.
At the age of 16 weeks, the mice were separated into three groups:
- The cytokine-treated macrophage group. The mice received macrophage treated with a specific set of cytokines.
- The untreated macrophage group. The mice received macrophages which had not been treated.
- The untreated group. The mice received nothing.
Only 25% of the mice who received the cytokine-treated macrophages developed Type 1 diabetes, compared to 83% in the other groups.
Dr. Harris said:
"The cell therapy was initiated just 2 weeks before mice developed clinical diabetes. At this stage few insulin-producing beta cells remain in the pancreas, yet we were able to protect these so that the mice never developed diabetes.
Such a successful late-stage intervention has never previously been reported and is a significant result of our study. At the time of their clinical Type 1 diabetes diagnosis, most human individuals have already lost most of their insulin-producing beta cells."
Written by Christian Nordqvist