An American research team, partly funded by JDRF, have developed a hydrogel material that increased islet survival and function after transplantation in mice.
The research, published in Science Advances, used a degradable hydrogel material combined with a protein called vascular endothelial growth factor (VEGF), to stimulate the growth of blood vessels into transplanted cells.
Islets are traditionally transplanted into the liver, however with this technique it is estimated that up to 50% of transplanted islets die within the first 24 hours. In this study, it was hoped that the hydrogel would stabilise the islets during transplantation and protect them from initial immune attack, while the VEGF would stimulate blood vessel growth to help them with long-term survival.
Scientists transplanted healthy islets coated in the hydrogel into three locations – under the skin, on the intestines and in a fat pad in the abdomen – in diabetic mice. They measured blood vessel growth, presence of immune “killer” cells and changes in glucose regulation.
Islet clusters transplanted with the hydrogel and VEGF developed many blood vessels and thrived in their new locations. Average blood glucose levels for the hydrogel-coated islets transplanted into the abdominal fat pad were significantly lower than those for islets in the other sites. Cell survival numbers were also highest in the abdominal fat pad. The equivalent structure in humans is called the omentum – a sheet of fat attached to the stomach and other organs.
JDRF is funding a separate ongoing early clinical trial in the US that is using a similar approach, but without the hydrogel. This trial recently published a successful transplant into the omentum of a 43-year-old woman who remains insulin-free 12 months post-transplant.
This research could lead to the identification of similarly suitable islet transplant sites in humans, supported by the use of a hydrogel. The improved success rate of islets could also mean that fewer pancreatic donors would be required to restore normal glucose regulation. This would reduce the demand for donors and the risk of rejection. In the long-term, this research could help to improve the safety and effectiveness of islet transplants for people living with T1D. The researchers will need to replicate the results using the hydrogel in other animal models and test the longer-term effects of the islet transplant, before potentially progressing to human clinical trials.
Transplantation research in Australia
Five JDRF-supported studies, including one funded by the JDRF Type 1 Diabetes Clinical Research Network (T1DCRN), are investigating techniques for more effective encapsulation and islet transplantation without the need for immunosuppression. Immunosuppression is normally required with an islet transplant to reduce the risk of the body rejecting the implant. For that reason and the need for human donors, the use of islet transplantation is currently limited to a small group of people. This research will help on the path to make islet transplantation a more widely available procedure to benefit more people with T1D.
Viacyte transplantation research
JDRF has partnered with Viacyte to fund research into a specialised encapsulation therapy that is currently at clinical trial stages in the US. The therapy, VC-01, involves the use of a specialised encapsulation device, called Encaptra, that holds the cells inside and protects them from an immune attack. You can read more about Viacyte here.