Under-Skin Transplants Show Promise for Type 1 Diabetes

In the journal Proceeding of the National Academy of Sciences, researchers from the Institute of Biomaterials & Biomedical Engineering (IBBME) at the University of Toronto in Canada describe how they developed and tested their subcutaneous transplant method in a mouse model of type 1 diabetes.

A significant feature of the study is that the transplant method uses tissue engineering to generate blood vessels that integrate with the host’s blood supply.

Insulin-producing cells are very sensitive to lack of oxygen, and inadequate blood supply is a problem that has dogged previous attempts to transplant them.

Type 1 diabetes destroys islet cells

Diabetes is a chronic disease that develops when the body cannot stop blood sugar or glucose getting too high.

If untreated, high blood sugar, or hyperglycemia, damages many parts of the body, including the heart, kidneys, eyes, nerves, and blood vessels.

Insulin – a hormone that is produced in the pancreas – is the body’s main regulator of blood sugar. It helps cells to take in sugar and use it for energy.

In people with type 1 diabetes, their immune system destroys the islet cells in their pancreas that produce insulin. In type 2 diabetes, the body produces insulin but cannot use it effectively.

There are approximately 30.3 million people living with diabetes in the United States. Type 1 diabetes, which accounts for around 5 percent of diabetes, is most often diagnosed in childhood, or during the teenage and young adult years.

There is currently no cure for type 1 diabetes and as yet, nobody knows how to prevent it. People with the disease need daily insulin injections to survive.

Challenges of transplanting islet cells

Transplanting of islet cells from donors is seen as a promising approach to treating type 1 diabetes. However, where to transplant them in the body – and then how to help them survive – is proving to be a major challenge to researchers.

“This makes it impractical to try and deliver islets to the pancreas: you would most likely be delivering it to a region of the pancreas that is secreting these enzymes,” he explains.

Other sites, such as the liver or the abdominal cavity, are equally unsuitable. Their “hostile” environments soon damage the cells. For example, in transplants into the portal vein of the liver, around 60 percent of the cells die in the first 48 hours.

To ensure that enough cells survive, the transplant requires such a large volume of cells that the patient would require islet cells from several donors.

Therefore, explain the researchers, there is a need for “a less hostile transplant site that is both minimally invasive and able to support a large transplant volume.”

Not only does the skin meet these requirements, it is accessible, and “makes islet transplantation a lot more manageable, especially if the patient responds negatively to the donor cells,” says Vlahos.

Islet cells embedded in tissue modules

For their study, the team took healthy pancreatic islet cells from rats and embedded them in tissue-engineered modules made from “collagen cylinders coated with endothelial cells.”

They then implanted the modules under the skin of mice that had been bred as an animal model of type 1 diabetes.

The transplanted islet cells – embedded in tissue-engineered modules – restored and maintained glucose control in the type 1 diabetic mice for 21 days.

An equivalent number of islet cells transplanted without embedding them in tissue-engineered modules had no effect on glucose control.

When they examined the transplant site, the researchers found that the implanted islets were surrounded by new blood vessels that were integrated with the host’s blood supply. They note that this is the first time that this has happened in subcutaneous islet transplants.

The team suggests that while the study is a step forward in using under the skin as a transplant site for type 1 diabetes treatments, it also offers a new way to explore “vascularization” – or generating a sufficient blood supply – in islet transplants.

“Pancreatic islets comprise approximately 1 percent of the pancreas, but require 15 to 20 percent of the blood flow to the organ. We needed to ensure adequate blood flow to the islets in order for this to work.”

Alexander Vlahos

The team also plans to try injecting islet cells into sites where they have used tissue engineering to grow a good blood supply network beforehand.

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