New findings could make pancreatic islet cell transplants more effective.
Immune rejection by the recipient is a major barrier to pancreatic islet transplants from donors becoming routinely available for the treatment of type 1 diabetes.
One way to overcome this is to place the islets — groups of insulin-producing cells — inside microcapsules made of a material that is less likely to provoke an immune response.
However, the process of microencapsulation can result in large numbers of empty capsules, which means a high volume of implant to achieve the required result. This increases the risk of immune reaction.
Now, researchers from the University of the Basque Country, in Spain, have developed a magnetic system for purifying the microcapsules that separates out the empty ones.
They describe the purification system, and how they tested its product in rats, in an International Journal of Pharmaceutics paper.
The study showed that, after implantation with “magnetically purified” islet microcapsules, rats induced to develop diabetes achieved and retained normal blood glucose levels for nearly 17 weeks.
“One of the drawbacks of islet transplants is the long-term use of immunosuppressant drugs to prevent the immune rejection of the transplanted islets; these drugs lower the patient’s defenses and entail serious medical complications,” explains first study author Albert Espona-Noguera, of the university’s School of Pharmacy.
Type 1 diabetes and islet transplants
Type 1 diabetes develops when the immune system destroys the insulin-producing cells in the pancreas. Without insulin, the body’s cells cannot absorb glucose from the blood to make energy. This results in dangerously high levels of blood sugar.
According to a 2016 BMJ Open Diabetes Research & Care study, the prevalence of type 1 diabetes worldwide is rising. In 2014, there were around 387 million people worldwide with diabetes, of which 5–10% had type 1.
Apart from very specific instances, islet transplants are not yet available for most people with type 1 diabetes. They still have to take insulin and monitor their glucose levels every day.
Microencapsulation promises to overcome two of the barriers to routine use of islet transplants: lack of donor islets and the need for recipients to be on immunosuppressants for the rest of their lives.
The system that Espona-Noguera and his colleagues have developed addresses both of these challenges. By increasing the proportion of capsules that actually contain islets, it makes better use of the scarce resource.
At the same time, by reducing the volume of implant that is necessary to produce the desired effect, it reduces the load that is likely to provoke an immune attack.
How the purification system works
The microcapsule purification system works by adding magnetic nanoparticles to the islets before microencapsulation.
Then, after microencapsulation, the microcapsules pass through the magnetic purifier. This separates the microcapsules containing magnetic islets from the empty, non-magnetic microcapsules.
The separation occurs in a 3D-printed microfluidic chip that has tiny channels containing magnets. The magnets are positioned so that when the microcapsules flow through the channels, the magnetic ones exit one way and the nonmagnetic ones exit another way.
Espona-Noguera says that the purification efficiency of the system is so great that they were able to reduce the implant volume of islets by nearly 80%.
Such a reduction has the potential to vastly reduce complications that can develop after implanting large volumes of microcapsules, he adds.
“In this work, we studied the functionality of the purified implants in diabetic animal models.”
Albert Espona-Noguera