3D scaffolds to optimize islet transplantation in type 1 diabetes
Dr. Gregory Korbutt's team at University of Alberta develop revolutionary technology that could eliminate the need for insulin injections.
Imagine a world where people with type 1 diabetes (T1D) would no longer have to inject themselves multiple times a day with insulin. For a select few, this world is already a reality. Islet transplants have revolutionized the treatment of T1D by allowing the transfer of islets of insulin-producing beta cells into patients whose pancreas no longer has the ability to produce insulin. JDRF-funded researcher and University of Alberta professor of surgery Dr. Gregory Korbutt and his team are working diligently to make islet transplants more widely available and functional through the use of their new 3D ‘scaffolding’ technology.
A scaffold is a polymer (a sheet of repeating molecules) that can be made biologically active, meaning it can be made to have an effect on a living being.
There are two challenges in making islet transplantation widely accessible: the availability of beta cells for transplant, and the challenge of keeping the islets of beta cells oxygenated and healthy. Dr. Korbutt and his colleagues are addressing these challenges by transplanting islets from animal sources (specifically, pigs) instead of humans, using their scaffolding technology to improve blood flow and oxygen to the transplant site, as well as incorporating proteins into the scaffolds that will help keep the cells healthy.
“Pigs are considered a potential source of transplantation of hearts, kidneys, islets, etc.,” says Dr. Korbutt. “Anatomically and physiologically, pigs are similar to humans. Researchers have been able to genetically engineer hearts from pigs, for example, without rejection. Adult pig islets have been difficult to isolate, but neonatal pigs are a good source.”
Finding a better transplant site
Typically, when islets are transplanted, they are infused to the portal vein in the liver, because transplant to the pancreas is just not possible. However, the liver is not the best site and a number of researchers have been investigating the idea of transplanting islets in other sites of the body, such as under the skin (also called ‘subcutaneously’).
“Transplanting under the skin is perfect and easy to perform, but this site does not typically have good blood flow,” explains Dr. Korbutt. “Without it, the transplanted islets do not receive enough oxygen and die. This is where the scaffolding technology can help. When implanted under the skin, a scaffold can allow the ingrowth of blood vessels in order to create a well-vascularized site.”
A scaffold enables more blood vessels to access the transplant site, which provides extra oxygen to the transplanted beta cells and helps keep them healthy. This technology works similarly to the scaffolds used in other types of transplants, such as skin grafts in burn victims.
Working to improve transplant success
Dr. Korbutt and his team have developed a ‘modifiable scaffold’ for islet transplant that not only allows the islets to be incorporated, but also for the addition of nutrient molecules, which promote cell growth and functionality. Other factors will similarly be included to help the islet graft survive and function. For example, the scaffolds are being designed to also deliver anti-rejection medications directly to the transplant site, which will improve success.
The team plans to first optimize their scaffold using transplantation of islets from neonatal pigs into diabetic immune-deficient mice to determine whether implantation under the skin is the best choice.
“We will also test this novel technology by implanting into muscle or fat, and refine the design to establish how many neonatal islets are required to achieve normal blood glucose levels in the mice,” says Dr. Korbutt. “The scaffold will then be further developed to support implantation of the neonatal pig islets into juvenile pigs.”
The investigators plan to report some of their preliminary research findings later this year at the International Pancreas and Islet Transplant Association meeting in Oxford, England.
The goal is to move to human clinical trials within the next few years. With the support of Dr. Korbutt’s $26 million Alberta Cell Therapy Manufacturing Facility (University of Alberta) for the production of cells for diabetes therapy as well as the Ingenuity Lab Nanotechnology Accelerator, where scaffolds are manufactured, this will be a very real possibility in the near future.