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University of Louisville procedure. Image via Business Wire

To those of us with type 1 diabetes, the idea of implanting healthy new insulin-producing cells into the pancreas sounds like the perfect fix.

Step right up! Get your new lifelong insulin-producing beta cells today…

Unfortunately, it’s not that simple. Let’s take a closer look at what this kind of transplant involves, in terms of time, cost, risks, and side effects.

Here are seven important things to know about cell transplants for diabetes:

The cells that produce insulin in a healthy pancreas are located in an area of that organ called the islets of Langerhans. Every islet cell found there contains alpha, beta, and delta cells.

“But you cannot just tease out the beta cells for a transplant. It’s hard enough just to isolate the islet cells. Instead, you have to purify the islet cells by weeding out the delta and alpha cells,” explains renowned endocrinologist Dr. George Grunberger, founder of the Grunberger Diabetes Institute in Michigan.

The alpha cells manage your glucagon needs to prevent low blood sugar — which have proven in research to be dysfunctional in those with type 1 diabetes.

Delta cells secrete somatostatin, another hormone that is largely involved with the function of your digestive and nervous system.

Lastly, beta cells are responsible for the production of insulin and a hormone called amylin. Insulin, as you likely know, helps your body make use of the glucose in your bloodstream for immediate or stored energy.

Amylin works in three ways that help manage your blood sugar during and after eating: it suppresses your liver’s release of stored sugar, it delays how quickly your stomach releases sugar into your bloodstream, and it helps you feel more satisfied after a meal.

The only thing being attacked by your immune system as a person with type 1 diabetes are the beta cells, which means a transplant should ideally focus on islet cells containing only beta cells. This is the challenge researchers are facing.

“And beta cells cannot reproduce — they can only grow in the fetus or immediately after you are born,” explains Grunberger.

Currently, if you want to be the recipient of an islet cell transplant, you have to participate in one of the many ongoing clinical trials.

“The FDA still considers an islet cell transplant as ‘experimental,’” explains Grunberger. “These research studies have been going on for decades, and there are clinical trials all over the globe and the United States.”

Find information on islet cell transplant clinical trials in the United States here.

“The transplant itself only costs $20,000, but you have to factor in the cost of purifying the islet cell prior to transplanting, and the post-transplant hospital stay, which can add up to approximately $138,000,” says Grunberger.

Since this type of transplant is only available via clinical trials, patients in those trials are not required to pay for the procedure. But if and when the procedure becomes more widely available, the cost will be prohibitive for many patients.

Researchers have pretty well perfected the implantation procedure, that involves these key steps:

  1. Secure a source of fully functioning insulin-producing islet cells from a “freshly” deceased pancreas.
  2. Extract, isolate and purify the islet cells so they contain only beta cells.
  3. Infuse the cells via gravity through a portal vein where the islet cells then settle in the liver.
  4. Protect the transplanted cells from being attacked by the immune system by introducing immunosuppressant medicines or encapsulation —- which is what newer technology like ViaCyte strives to do.
  5. The patient should begin producing insulin successfully within a few weeks after the transplant, but it can take up to 3 months for some.

The very first islet cell transplants were conducted in 1989, and the success rate was very low, with only 8 percent of patients remaining off insulin by the end of the first year.

The groundbreaking “Edmonton Protocol” was published in 2000 in the New England Journal of Medicine. This protocol eliminated the use of steroids and has become the standard for islet cell transplant procedures today. It involves “localized” immunosuppression rather than “whole-body immunosuppression.”

But the need for immunosuppression to ward off the immune system attack on transplanted cells remains the weakest link in all of this, explains Grunberger. That’s because the side effects that come with immunosuppression can be dangerous and lifelong.

The University of California, San Francisco (UCSF) is working with a drug called efalizumab and reports that it’s one of the most effective options for suppressing the specific immune system cells at play here: effector T cells and TREG populations.

In case you’re wondering where doctors put the cells, that would be the portal vein, located in the upper right quadrant of your abdomen, that drains into your liver. It’s used for many other procedures which means the process for transplanting and delivering into this vein is well established, explains Grunberger.

“The portal vein is the easiest place to reach because it’s large and it provides adequate blood supply. Once transplanted, the islet cells need both oxygen and glucose for survival, which means exposing the cells to healthy blood is critical for their survival (or) the cells can get destroyed… It doesn’t make a difference where you put those cells as long as there is an adequate blood supply.”

First, it’s important to realize that a standard islet cell transplant isn’t a “one and done” type of procedure. Your immune system will continue to attack and destroy islet cells despite immunosuppression, which means you’ll need recurring transplants every few years based on your body’s personal success rate.

Evolving technology like ViaCyte’s islet cell capsule aims to change this, but it’s at least a decade away from being widely available.

Despite the need for recurring transplants, today’s success rates are high, says Grunberger, “but how do you measure success?”

He feels that success is based on whether a patient must continue taking insulin injections via pump, pen, or syringe, but many studies base success on the achievement of an A1C under 7.0 percent.

Many patients may raise an eyebrow at this definition of success since today’s diabetes management technology and insulin makes achieving an A1C under 7.0 percent reasonably doable.

Grunberger reports the following as typical results of an islet cell transplant:

  • At 1 year post-transplant, approximately 75 percent of patients are still “insulin-free.”
  • At 2 years post-transplant, approximately 40 to 50 percent of patients are still “insulin-free.”
  • At 3 years post-transplant, approximately 10 to 30 percent of patients are still “insulin-free.”

Eventually, you will need another transplant, likely within 3 years. As long as you continue to qualify for the clinical trial, you can continue to receive transplants.

“Initially, yes, the success rate is virtually 100 percent, but the rate of islet cell destruction after a transplant varies from patient to patient,” adds Dr. Grunberger.

“I had one patient who has undergone three consecutive transplants, and she had been living with type 1 diabetes for over 40 years. She was initially ‘insulin-free’ after each transplant.”

In one rare case at UCSF, one patient had to be taken off immunosuppression therapy following her transplant due to developing the latent Epstein-Barr virus. Oddly enough, she fully recovered and continued to be “insulin-free” without immunosuppression for an entire year.

The side effects of a transplant really come down to the side effects of the immunosuppression drugs.

While today’s transplants use more localized immunosuppression to affect just the immune system rather than your entire body, the risks and side effects that come with this range from mild to significant.

“All patients complained of nausea immediately after the islet cell infusion which resolved over 24 to 36 hours,” notes a 2011 study published by the American Journal of Transplantation that focused on one particular type of immunosuppression drug, efalizumab, most commonly used in islet cell transplants.

Other noted side effects that range from mild to severe can include:

  • rash or redness on the skin at the injection site after the first dose
  • diarrhea
  • accidental liver puncture that resolved on its own
  • partial portal vein thrombosis which resolved with blood thinners
  • elevated Epstein-Barr virus (EBV) levels, indicating infection
  • neutropenia (low neutrophils count, which increases the risk of infection)
  • thrombocytopenia (low blood platelet count, which prevents healthy blood clotting)
  • symptomatic oral ulcers, which are painful ulcers in the mouth

So should you sign up for an islet cell transplant clinical trial, if you had the opportunity?

If you are a relatively healthy individual who meets the eligibility criteria, it may be worth your while. Just know that it’s not an easy fix for type 1 diabetes. Instead, it may provide significantly more stable blood sugar levels but it also inevitably comes with other risks and medical issues.

That’s because suppressing the immune system inevitably bears significant risk, and is the greatest obstacle modern medicine is working to overcome when it comes to successfully transplanting anything, including islet cells.