The Pouch That Improves Type 1 Diabetes Islet Cell Transplants

In the search for a cure for type 1 diabetes, many scientists and researchers have converged around one general approach: the implantation of laboratory-grown islet cells that have somehow been shielded or hidden from the immune system. But the exact details of this potential cure are far from settled, and many different groups are attacking the solution from different angles. It’s quite possible that a real functional cure — if we ever get one — will combine innovations from several different labs that aren’t working together today.

Sernova, a Canadian biotech firm, hopes to contribute with its Cell Pouch System, a medical pouch that can be surgically implanted under the skin to house implanted pancreatic islet cells. The Cell Pouch, ideally, will allow transplanted cells to better integrate with the body, offering better safety and efficacy. CEO Cynthia Pussinen walked Diabetes Daily through Sernova’s innovation.

There hasn’t been much buzz about Sernova in the media, but the company can boast of some impressive results. “We have patients who have been insulin-independent for close to four years,” says Pussinen.

Islet Cell Transplants

The islet cells, also known as the islets of Langerhans, are the parts of the pancreas that produce hormones. Islet cells are really cell clusters, not individual cells. These clusters are where you’ll find the Beta cells, the insulin-secreting cells that are destroyed in the autoimmune attack that causes type 1 diabetes, and several other types of endocrine cells that are critical for proper metabolic function.

We know that islet cell transplants can work. Some transplant recipients have remained free of insulin therapy for many years following the procedure. But the procedure is associated with a variety of issues that have prevented its widespread adoption as a therapy for type 1 diabetes:

As of today, all islet cells must be harvested from the bodies of deceased organ donors, strictly limiting the supply.
Transplant recipients require anti-rejection drugs for their new cells from the immune system. These drugs have a severe side effect profile and are toxic to the transplanted cells.
The transplants don’t always work — many patients experience only short-term benefits.

The cell pouch is mostly intended to solve the last of those problems, which could help make islet cell transplants more effective and reliable and therefore more viable.

Introducing the Cell Pouch

The cell pouch is an actual pouch that is inserted under the skin of the abdomen. “It’s about the size of a credit card, only a few millimeters thick, made of a very flexible polypropylene material,” says Pussinen. “We put the islet cells into the cell pouch. Patients report that they can’t even feel it.” The surgery only takes about 15 minutes.

The cell pouch’s materials have been FDA-approved for permanent use in the body. One very early Sernova volunteer has had a cell pouch in their body for 14 years with no ill effects. “You don’t see any fibrosis [scarring] of the tissue, the tissue around the pouch has remained healthy,” says Pussinen.

The cell pouch is intended to be an alternative to the prevailing method of implanting islet cells directly into the portal vein, which allows them to settle in the liver. With this, the dominant protocol, “they don’t have long-term survival or engraftment in many cases,” says Pussinen. “And this is where the cell pouch is quite different.”

The cell pouch doesn’t just sit there underneath your skin — the body actually grows around it, spreading blood vessels across its surface: “It becomes highly vascularized, it’s kind of like the roots of a tree growing around it. It forms a very nice home for the islet cells.”

“This is a much more stable approach. It’s safer, it’s tolerated far better.”

Another benefit of the cell pouch is that it can be removed. This has already happened once after it was learned that a single study participant had received a transplant of islet cells that were contaminated with candida albicans yeast. (This happens sometimes. Organs for donation cannot be perfectly evaluated for sterility before transplantation occurs). The transplant team was able to explant the cell pouch without any problems.

“It’s another big benefit — if something does happen, you can take it out. With injections into the portal vein alone, once those cells are in there, you’re not getting them out. If something’s bad, you’re stuck.”

The Results

The early results suggest that the cell pouch system may improve the outcomes for people with type 1 diabetes undergoing islet cell transplants. Sernova recently announced the interim results from its Phase 1/2 trial of the system: Six patients have been successfully implanted with the cell pouch system.

Five of those six are now insulin-independent
All six have achieved A1C values in the non-diabetic range (less than 6.5 percent).

The results are even better than Sernova expected — this early trial was only designed to assess the safety of the pouch system. Patients in a second cohort have been implanted with a higher-capacity pouch to help determine optimal dosing.

Pussinen says that islet cell transplants could become a much better alternative than the status quo of insulin injections for people with type 1 diabetes: “Insulin therapy is really, in my opinion, an incomplete approach. You’re not addressing the alpha cells or the delta cells, glucagon, or somatostatin. With islet cell therapy, this is a very holistic approach and can achieve what we call a functional cure.”

The Future

The cell pouch still has many hurdles to jump, and is certainly years away from FDA approval, if it gets there. And even if new larger studies confirm the pouch’s positive effects, there’s still plenty of work to be done.

While the cell pouch may help solve one issue related to islet cell transplantation, it doesn’t yet solve the others — the need for immunosuppressive drugs and the limited supply of organ donors. Because of these issues, islet transplants are currently limited to only the most desperate cases, typically those with severe hypoglycemia unawareness and a history of dangerous hypoglycemic events.

Sernova has plans to address both problems.

The company has partnered with Evotec, a German firm that works with induced pluripotent stem cells (iPSCs). A similar approach has proven very successful for Vertex Pharmaceuticals, the business that is widely acknowledged to be the closest to a type 1 diabetes cure. These cells are grown in a laboratory and can be induced to become islet cells, which would allow Sernova to stop relying on organ donors. Lab-grown islets can also be frozen for transportation, removing the need for helicopters, ambulances, and special couriers often needed to transport organs for transplant.

The cell pouch system does not, in and of itself, reduce the need for immunosuppressive drugs, but it could help make it easier to protect transplanted islet cells. Sernova is currently laying the groundwork for implanting islets that have been “micro-encapsulated” in a conformal coating that could offer immune protection. Pussinen calls it a type of “shrink-wrapping.”

Immunosuppression has been called the final piece of the puzzle of a type 1 diabetes cure. Vertex is currently experimenting with its own encapsulation technique, but its success is far from assured.

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