London, Canada-based Sernova is taking on today’s islet cell transplant challenges and looking to give islet cell recipients better chances of realizing insulin-independence for greater periods of time and in the long term, offer greater utilization of the procedure to a larger patient population.

By: John Parkinson, Clinical Content Coordinator,

Sernova would like to address all facets of islet cell transplantation with a suite of technologies. The Canadian company wants to create a new standard surgical protocol with the use of its Cell Pouch System; replace the immunosuppressant agents being used now with its Sertolin cell platform; and lastly provide stem cells in place of donated islet cells for infusion.

These are no small feats, especially considering no one thus far has developed products for any of these facets.

One of the ongoing challenges for islet cell transplantation today is that many of the cells infused into patients are not viable post-transplant. In wanting to enhance the islets’ viability, Sernova has developed its Cell Pouch System (an illustration of it shown here), which creates a suitable environment inside peoples’ bodies for the transplanted islets to exist and function like the pancreas normally does in people who do not have diabetes.

The process works as such: the Cell Pouch is implanted into the body just under the skin prior to the islet cell transplant. Once the Cell Pouch has vascularized over the course of a few weeks, the islet cells are then infused into the Cell Pouch site.

Leading the company is President and CEO Philip Toleikis, PhD (pictured below). talked with Toleikis about how the individual technologies work and how the company is going about their ambitious plans to offer a comprehensive, efficacious way to deliver islet cell transplantation. Can you provide an overview of what the Cell Pouch System is?

Toleikis: It is an implantable medical device in which therapeutic islet cells are placed. When the device is placed under the skin of the abdomen, it then becomes a part of the natural environment of the body with the formation of small blood vessels and tissue. This is essential because each islet is required to have a blood supply. Is the Cell Pouch implanted and then eventually removed?

No. It is a polymer device which can exist in the body permanently. It forms an organ-like environment. We implant the Cell Pouch; then within approximately 2 to 4 weeks we transplant the islets. Once the transplanted islets are in the body they will function similarly to that of the pancreas in controlling the diabetes.

There are tissue chambers in our device and once the islets are placed into the device, they release growth factors which stimulate more blood vessel developments. These vessels surround the islets the way they do in the pancreas and that is what allows the communication between the blood vessels and the islets—and then they begin to function. 

We have proven this works and is safe in multiple animal models, taking away the need for insulin injections, and that is why we are moving to perform the clinical trials on people. You had mentioned that the Cell Pouch was made up of a polymer. Does it contain any other compounds?

Toleikis: It is a number of different polymers, actually. We have worked with device engineers, surgeons, and biologists to develop the device to match the needs of the body and surgeons. We have not used any special growth factors because we want the body to act naturally when the Cell Pouch is introduced into it.

We are using polymers that have been approved by the FDA for long-term use in the body. As Sernova has ambitious plans to eventually help everyone with diabetes, can you explain how this device will help people with type 1 and type 2 diabetes?

Toleikis: The first group of patients we are studying are those with type 1 diabetes who have hypoglycemia unawareness. These are patients with unstable diabetes. 

The islet transplant treatment that is currently being used is called the Edmonton Protocol. This procedure is done by injecting donor islets into the portal vein.

What we are first developing is a more efficacious and safer location for the islets. Our first study in humans, which is currently underway, is assessing the Cell Pouch with the best standard of care anti-rejection protocol.

As we move forward, we are going to be replacing the anti-rejection drug protocol with our Sertolin product. [Editor’s note: All transplant patients take immunosuppressant drugs immediately after the transplant and while they remain insulin-independent.] This will allow us to treat a much larger population of patients, because we will remove the ongoing challenges with anti-rejection drugs patients are taking now.

Over time, we plan to use insulin-producing stem cells, and this again, with more cells to implant, would allow us to offer the procedure to a much larger number of people with diabetes. Who are you going to be using the stem cells for?

Toleikis: Over time, we plan to treat many more patients with insulin-dependent diabetes. To do this, surgeons will transplant islets into the Cell Pouch from an unlimited source of cells such as insulin producing stem cells combined with our local anti-rejection technology (Sertolin). This could then become the new standard of care for insulin-dependent diabetes. How do you envision replacing the Edmonton protocol?

Toleikis: With the Edmonton Protocol, Dr. James Shapiro [one of the developers of the protocol] isolates the islets from the donor pancreas and then injects them into the portal vein of the liver. Instead of utilizing the portal vein, we are working with Dr. Shapiro to infuse the islets into the Cell Pouch.

When you infuse the islets into the portal vein there is a major inflammatory response, and it kills an estimated 60 to 70 percent of the islets. By infusing the islets into the Cell Pouch, we are establishing a natural environment for the islets. That way, we can expect them to survive long-term, like they do in the pancreas.

Another point to consider is that when you infuse islets in the portal vein you can’t image them; surgeons are very interested in imaging the islets to determine how they are functioning over time. 

It simplifies the procedure; and you also decrease the number of islets needed for transplantation. Typically you need to use 2 to 4 donors’ worth of islets to be able to achieve insulin-independence in patients. In our animal studies, we have shown we can put in a fraction of that amount into our Cell Pouch. This is because we believe the islets are surviving in a much more natural environment.  

There is a phrase, `marginal islet mass,` which essentially means surgeons infuse a smaller amount of islets to achieve insulin independence. And we have been able to do this because the Cell Pouch System is more efficient. As you received approval from Health Canada [Canada’s medical regulatory agency] to proceed with the Cell Pouch System in islet cell transplantation, can you explain how far along you are in the process?

Both Health Canada and the University of Alberta Ethics Review Board board have approved us to start the study. We are enrolling patients and thus have started the clinical trial. 

[Editor’s note: Shortly after this interview, Sernova in collaboration with the University of Alberta announced it had performed the world’s first islet cell transplant using the Cell Pouch. To read further about it go here.] Are you going to be working the University of Alberta only, or are you planning to work with other medical centers that perform the procedure?

Toleikis: We are conducting the first clinical trial with Dr. Shapiro at the University of Alberta to make sure the procedure is safe and effective. Once we obtain safety and efficacy data, then the plan is to start to move the procedure into other sites. We are interested in expanding the study into the United States and Europe. We are in talks now with regulatory bodies in those areas in order for that to occur when we are ready. It is important for us to make sure the Cell Pouch is working well and is producing good results in the first patients. What are your hopeful expectations for the Cell Pouch System?

Toleikis: It has been shown that islet cell transplants can reduce the side effects and potential comorbidities of diabetes because they control glucose much more tightly than insulin injections.This is important for people with diabetes. Regarding the current state of islet transplantation, there are about 30 centers around the world currently conducting this procedure using the Edmonton Protocol. It is a costly and time-intensive procedure—whereby surgeons have to wait for the pancreas from organ donors to come in, and patients have to travel, sometimes long distances to these limited centers. We are working to move that to a position to where we have the three technologies—Cell Pouch, stem cells of an unlimited supply, and the protector cells (Sertolin)—which we hope to supply to any surgeon who will perform the simple procedure. We want to eventually be able to offer our technology on an outpatient basis to any medical center or hospital that wishes to perform it.

This would enable us to treat millions of patients with diabetes around the world. That is our long-term goal.

Of course as a small company, we are taking this in steps, but we plan to grow as the technology becomes successful and this will enable the process to move faster. Turning to Sertolin, which we have referenced above here, can you explain what it is and how it works?

Toleikis: There are sertoli cells in the body, and they protect the body from attack. The sertoli cell lines are located in the seminiferous tubules in males. These cells protect sperm cells, because sperm cells have only one half of the genetic makeup, and without this protection, these cells would be destroyed by the immune system.

We have taken these sertoli cells and mixed them in with islets and shown that they will protect the islets. The sertoli cells release a number of chemical factors that prevent the white blood cells from attacking the therapeutic cells. There is stronge scientific evidence that this works.

Our plan is to take the sertoli cells combine them with the islets when they get transplanted into the Cell Pouch. How are the sertoli cells developed?

Toleikis: At first we would have human donors. The sertoli cells are isolated from the tissue. Eventually, we would like to obtain an unlimited supply of these cells too. You had mentioned co-culturing the sertoli and islets. Can you explain how this process will work?

Toleikis: Surgeons would receive separate vials of Sertolin and islets and a Cell Pouch. The Cell Pouch is placed under the skin; the surgeon would then take the islet and Sertolin cells together and infuse them into the Cell Pouch—once the Cell Pouch was incorporated within tissue. We would expect the Sertolin cells to function rapidly in protecting the islets. Which patients would the Sertolin benefit?

Toleikis: Everyone who gets a transplant. Just like our plans with the Cell Pouch, we would treat type 1 people with hypoglycemia unawareness first; then other type 1s; and lastly, we would  work with people with type 2 diabetes who are insulin-dependent. This is about 27 percent of the type 2 patient population. 

People with type 2 diabetes are still getting the serious side effects associated with uncontrolled blood sugar, but with this technology it could potentially  give them better control and reduce the incidence of side effects. Have you perfected Sertolin yet?

We have done animal studies to show that it works. However, we have to do formal preclinical studies too. Afterwards, we will present them to the regulatory bodies with our current data, and then we can move forward with the clinical trials, pending regulatory approval.

It also depends on the capital markets, because we need funding to support the trials. And what is the timeline for the Cell Pouch and Sertolin to be used as part of a treatment protocol if all goes well?

Toleikis: As I had mentioned previously, we are in the process of talking to regulatory agencies right now, and we are looking at approximately five years to get approval of the pouch—it could be a little less. And with the Sertolin technology, it would be some time after that.

It will depend on the discussions with the regulatory agencies, and the efficacy and safety data in our clinical trials. Lastly, how far out is the stem cell technology?

Toleikis: The stem cell technology is very promising but it is still quite a ways out into the future. This is the reason for Sernova’s tiered approach to our technology development—to reach people with diabetes as soon as possible with the Cell Pouch and then expand the number of treatable patients with our overlaying technologies improving the safety and availability of insulin-producing cells.