Researchers develop method to improve artificial islet transplantation success rate

Researchers from the Institute of Biomaterials and Biomedical Engineering (IBBME), Chemical Engineering, and the Donnelly Centre have developed a method to fine-tune the cellular composition of artificial islets – the organ responsible for regulating blood glucose in the body. This advance could improve the success of implantable islets to treat people living with diabetes. The study was led by senior graduate student Dr. Alexander Vlahos in Dr. Michael Sefton’s lab, and the findings were recently published in the journal Biomaterials (DOI: 10.1016/j.biomaterials.2019.119710).

In a healthy individual, pancreatic islets are responsible for secreting insulin – a vital molecule that regulates glucose level in the human body. This function is severely dampened in those living with diabetes, where significantly lower insulin production can lead to blindness or kidney failure.

Recent advances have enabled researchers to implant artificial islets (called pseudo-islets) directly under the skin to regenerate normal glucose modulation in animals. This provides a longer lasting and hands-off method for diabetes management as opposed to repeated insulin injection.

“The success rate of transplantation is dependent on the health of the pseudo-islet,” says Dr. Alex Vlahos, the lead author of the publication, “Most of the islet cells die soon after transplantation. In our study, we developed a method to fine-tune the size and composition of the pseudo-islet to improve the success of implantation.”

The researchers first harvested donor islets and isolated the cells responsible for insulin production. The key was to next recombine them in a 3D environment to resemble an islet. These artificial islets were then reintroduced into a diabetic animal to restore glucose level. The authors also observed proper blood vessel formation, a hallmark of healthy regeneration of an organ.

“The next step is to evaluate the therapeutic impact of human artificial islets,” says Sean Kinney, a co-author on the study, “The ultimate goal is to implant these islets into humans and have them last a decade. But there’s still quite a few barriers we have yet to overcome.”

Improvement to transplantation success is crucial for its translation into the clinic. Due to the scarcity of islet donors, this is not yet a widely adaptable method. Normally one islet transplantation would require three donors, but if the engraftment rate is better, three donors could be reduced to one. This can effectively increase the number of patients this method can serve.

“Creating artificial islets gives us the opportunity to create an organ that is better than what nature has provided.” says Dr. Michael Sefton, the corresponding author on this research, “Islets have evolved to control our blood sugar and we have learned to transplant them. We can now engineer them to be better than nature when transplanted – to reduce their oxygen consumption per unit of insulin produced or to better withstand the host response.”