Subdermal implant could boost islet cell therapy for diabetics

While islet cell transplants allow some diabetics to forgo daily insulin injections, those people have to take immunosuppressive drugs in order to keep the cells from being rejected. A new implant, however, could administer the drugs for them – and with fewer side effects.

In Type 1 diabetes, the islet cells produced by the pancreas are destroyed by an autoimmune reaction. They therefore aren’t available to travel via the bloodstream to the liver, where they would have produced blood-sugar-regulating insulin.

As a result, patients typically have to give themselves daily insulin injections. Not only is this task painful, but it can also often be difficult to work into one’s busy routine every single day.

One alternative involves harvesting islet cells from a deceased donor, and transplanting them into the patient’s liver. For several years, those cells proceed to produce insulin, eliminating the need for daily injections.

Unfortunately, though, in order to keep the body’s immune system from identifying the introduced islet cells as foreign bodies that must be neutralized, the patient has to take immunosuppressive drugs on an ongoing basis. Because these drugs are taken orally, and are thus distributed throughout the body, relatively large doses are required – and the larger the dosage, the more severe the unwanted side effects, such as a compromised overall immune system.

It was with these problems in mind that scientists at Houston Methodist Hospital created an experimental implant known as the NICHE (Neovascularized Implantable Cell Homing and Encapsulation).

Similar in size to a US quarter-dollar coin, the flat polyamide-bodied device is designed to be implanted under the skin. It contains two reservoirs – a rectangular inner one that contains islet cells, and a U-shaped outer one (which goes around three sides of the inner reservoir) that contains immunosuppressive drugs. A mesh “roof” on the inner unit allows blood vessels to grow into it, supplying the islet cells with much-needed oxygen.

Both reservoirs gradually release their payloads for weeks at a time, through porous membranes along the sides of the NICHE. The islet cells are thus taken up by the bloodstream and relayed to the liver, while the immunosuppressive drugs provide an immune-blocking effect only right where it’s needed – this means that a much smaller amount of those drugs is required.

When the implant needs refilling, more cells or drugs are injected into it simply by poking a hypodermic needle through the patient’s skin and through a self-sealing silicone plug at the end of desired reservoir.

In tests performed on diabetic rats, the NICHE reportedly restored normal blood glucose levels and eliminated Type 1 diabetes symptoms for over 150 days, without producing any severe side effects. The device was refilled once every 28 days, although the scientists are now working on a version that could go for up to six months between refills when used in humans. It’s even possible that changes in drug formulations could extend those intervals to just once a year.

“A key result of our research is that local immunosuppression for cell transplantation is effective,” said the lead scientist, Prof. Alessandro Grattoni. “This device could change the paradigm of how patients are managed and can have massive impact on treatment efficacy and improvement of patients’ quality of life.”

The research is described in a paper that was recently published in the journal Nature Communications.

Source: Houston Methodist

While islet cell transplants allow some diabetics to forgo daily insulin injections, those people have to take immunosuppressive drugs in order to keep the cells from being rejected. A new implant, however, could administer the drugs for them – and with fewer side effects.

In Type 1 diabetes, the islet cells produced by the pancreas are destroyed by an autoimmune reaction. They therefore aren’t available to travel via the bloodstream to the liver, where they would have produced blood-sugar-regulating insulin.

As a result, patients typically have to give themselves daily insulin injections. Not only is this task painful, but it can also often be difficult to work into one’s busy routine every single day.

One alternative involves harvesting islet cells from a deceased donor, and transplanting them into the patient’s liver. For several years, those cells proceed to produce insulin, eliminating the need for daily injections.

Unfortunately, though, in order to keep the body’s immune system from identifying the introduced islet cells as foreign bodies that must be neutralized, the patient has to take immunosuppressive drugs on an ongoing basis. Because these drugs are taken orally, and are thus distributed throughout the body, relatively large doses are required – and the larger the dosage, the more severe the unwanted side effects, such as a compromised overall immune system.

It was with these problems in mind that scientists at Houston Methodist Hospital created an experimental implant known as the NICHE (Neovascularized Implantable Cell Homing and Encapsulation).

Similar in size to a US quarter-dollar coin, the flat polyamide-bodied device is designed to be implanted under the skin. It contains two reservoirs – a rectangular inner one that contains islet cells, and a U-shaped outer one (which goes around three sides of the inner reservoir) that contains immunosuppressive drugs. A mesh “roof” on the inner unit allows blood vessels to grow into it, supplying the islet cells with much-needed oxygen.

Both reservoirs gradually release their payloads for weeks at a time, through porous membranes along the sides of the NICHE. The islet cells are thus taken up by the bloodstream and relayed to the liver, while the immunosuppressive drugs provide an immune-blocking effect only right where it’s needed – this means that a much smaller amount of those drugs is required.

When the implant needs refilling, more cells or drugs are injected into it simply by poking a hypodermic needle through the patient’s skin and through a self-sealing silicone plug at the end of desired reservoir.

In tests performed on diabetic rats, the NICHE reportedly restored normal blood glucose levels and eliminated Type 1 diabetes symptoms for over 150 days, without producing any severe side effects. The device was refilled once every 28 days, although the scientists are now working on a version that could go for up to six months between refills when used in humans. It’s even possible that changes in drug formulations could extend those intervals to just once a year.

“A key result of our research is that local immunosuppression for cell transplantation is effective,” said the lead scientist, Prof. Alessandro Grattoni. “This device could change the paradigm of how patients are managed and can have massive impact on treatment efficacy and improvement of patients’ quality of life.”

The research is described in a paper that was recently published in the journal Nature Communications.

Source: Houston Methodist