Subcutaneous Islet Transplant Provides Safer, Efficient Path for Type 1 Cure

Islet cell transplants as a mode for curing type 1 diabetes have become a popular research focus over the past decade despite the fact that scientists have been using this procedure, with minimal success, for almost sixty years.

The issues that continue to plague this process beg the question: Is an effective and affordable islet transplant procedure even possible?

Scientists out of the University of Pennsylvania think so.  Their most recent advancements hold promise for a simple, low-risk transplant option with a potential for big rewards.

Collagen Matrix Protects and Nourishes Transplanted Cells

The traditional method for transplanting islet cells involves boring a hole in the femoral artery and threading an infusion of islet cells through the portal vein in the liver.

The liver provides a natural, blood-rich matrix for the new cells to grow in, but the procedure itself comes with dangerous complications like bleeding, thromboses, and infection. And, despite the optimal conditions in the liver, mass islet cell die-off is common.

Implanting the cells directly under the patient’s skin comes with far fewer risks than more traditional procedures, but the risk of islet cell death is even greater.

Or at least, it used to be, before the Penn researchers developed a unique method of protecting and nurturing the transplanted islet cells.

In their paper published in Nature Metabolism, the scientists describe how they created an Islet Viability Matrix (IVM) using collagen and cartilage. The matrix resembles the environment found in the pancreas where islet cells normally grow.

The IVM not only promotes vessel growth to bring nourishing blood to the new cells, but it also appears to suppress signaling that would normally cause autoimmune response cell death.

Positive Early Results in Animal Models

When the islet-filled IVM was transplanted under the skin of diabetic mice, their blood sugar normalized within a day. And the effect lasted for months until the mice were sacrificed so that the health of the matrix graft could be investigated.

In primate trials, similar positive results have been seen with one macaque monkey now diabetes-free for more than two years.

Human trials have not yet begun, but the researchers are optimistic that using donated human islet cells in the IVM will also result in robust, fully functioning insulin-producing cells when transplanted under the skin of type 1 patients.

Refining the Method for Safer Outcomes

While this new method of islet cell transplantation addresses one of the major challenges of the procedure–the risk associated with the transplant operation itself–it still fails to overcome the two biggest drawbacks of the process.

1. The need for life-long immunosuppressant drugs
2. The lack of available islet cells for transplant

Avoiding immunosuppressants is the next challenge on which the Penn researchers are focusing. 

They hope to work further with study co-author Dr. Bernhard Hering to utilize his methods for immunosuppressive-free, apoptosis-mediated islet cell transplantation using their newer, less invasive IVM method.

Another team of researchers out of the Salk Institute recently achieved successful islet cell transplantation without the use of immune-suppressing drugs, proving that such a feat is possible by more than one means.

Other Research in Islet Cell Transplantation

The Penn and Salk Institute researchers aren’t the only ones looking to refine this decades-old method in their hunt for a diabetes cure. Here are three more promising islet cell transplant methods currently being studied.

• Teams from the universities of Arizona and Minnesota teamed up to create an oxygen-rich, islet-filled “tea bag” with the potential to decrease the number of islet cells needed by four times the current amount. Considering how hard it is to successfully harvest healthy islet cells from donors, this is a huge step toward making islet transplants widely available.
• The Sernova Cell Pouch provides a safe, vascularized environment for islet cells that can be implanted through a small incision in the skin. With the addition of local immune protection technologies, the researchers hope this method will allow for less invasive islet transplants without the need for systemic immunosuppressants.
• One fascinating approach to islet cell transplantation doesn’t use islet cells at all. ViaCyte’s Encaptra cell delivery system is filled with beta-cell precursors that mature into insulin-producing cells once the device is implanted and vascularization occurs. This method sidesteps the need for immunosuppressants and islet cell harvesting.

While no one method for islet cell transplantation appears to overcome all the hurdles associated with the current process, many researchers have found unique ways of making this procedure safer, more effective, or more attainable. Finding the one method that achieves all three is only likely to be a matter of time.