The research into an encapsulation device that contains functioning beta cells such as those in a pancreas is still going strong. Viacyte is now working with three different Encaptra cell delivery devices. These devices enable transplantation of pancreatic precursor cells that can go on to mature into fully functioning cells found in a healthy pancreas. Precursor cells are partially differentiated cells called progenitor cells that can become beta, alpha, and delta cells of the pancreas (more on this below). Progenitor cells have many potentials uses in medicine.

Viacyte was the first to develop an islet cell replacement therapy contained inside a device that has the potential to have functioning beta cells while also providing protection from the autoimmune attack. They were the first to achieve curative levels of insulin in animal models, and then the first to be successful with this in humans. This was proof of concept that this could work. Viacyte is working to take larger steps by partnering with the company W.L. Gore, and creating future new devices with CRISPR Therapeutics to produce devices capable of replacing the pancreatic cells needed in T1D.

Let us first go back and start with how we were able to get to this point in research. Islet cells consist of three different types. Said simply, beta islet cells produce insulin, alpha islet cells produce glucagon, and delta islet cells produce somatostatin. Most of us are familiar with insulin and glucagon. The role of somatostatin has an inhibitory effect on insulin and glucagon. All work together in consort to give a normal blood glucose level. Through cadaver islet cell transplants we were able to see that by replacing these cells, we can return to a life without T1D. There are many limitations on cadaver islet cell transplant due to the low numbers of available cadaver pancreases available, the need to keep the islet cells viable and healthy before transplant, and the high cost of transplanting an organ. Hypoglycemia unawareness is often a requirement for qualification for a cadaver islet cell transplant.

Viacyte is working on overcoming the body’s response to an implanted device. Their cells, called PEC-01 cells, are pancreatic precursor cells but not stem cells. They can further change into the three pancreatic islet cells: beta, alpha, and delta. They are able to place these cells in the pouch of their encapsulation device. This pouch is put just under the skin in the abdomen or torso. In order for this to be successful, the pouch needs to have successful engraftment in the area of placement. Engraftment is when the blood supply to these cells becomes well established and the body has adapted to the presence of these new cells within the pouch. The cells that are in this pouch do remain inside this pouch.

There are three different devices. The difference in these devices comes down to how they get their blood supply and how they are protected from the immune system:

PEC-Encap allows nutrients to enter the pouch and the blood vessels that are outside of the pouch. Nutrients and oxygen can diffuse through the membrane. This membrane is being studied in partnership with the company W.L. Gore.

PEC-Direct have blood vessels going directly into the pouch, which has direct vascularization. This provides a direct supply of nutrients to the cells. This device does require immunosuppression due to the flow of blood through the device and immune cells being able to cross into the device.

PEC-QT is basically the same Encaptra device with cells that are modified to avoid the attack by the immune system. This technology is currently being developed in collaboration with CRISPR Therapeutics.

There are some design differences, and during this research and development process they are able to do tissue staining and really see these new beta cells producing insulin. When the device achieves engraftment and insulin production has begun, they are also able to see an increase in C-peptide production. This is the biomarker for insulin production. A biomarker is a measurable substance whose presence is an indicator of a biological state or condition. This marker is seen in patients that previously had no C-peptide activity. For this reason, in a study involving an Encaptra device, you would need to be negative for C-peptide production when enrolling.

With the first devices, initial studies did see an aggressive foreign body response (FBR). With newer devices they can now limit that reaction and are currently testing a new membrane. This newer membrane does not cause a reaction within the body, is stable, and holds cells successfully. It is able to protect cells from immune attacks while allowing protein and nutrients to go through. Insulin is then transported outside of the device. With the new W.L. Gore company membrane, this device is also showing an increase in insulin output.

There will continue to be development on new devices. There will be new clinical trials available on these devices to see if we can see therapeutic benefit. You can find these trials on clinicaltrials.gov and on the clinical trials chart on the JDRF Minnesota and Dakotas website. For information on the trial currently taking place at the University of Minnesota, the brochure link is provided here VC02-101 Study 2-Pager 3Dec2020 FINAL. For this clinical trial, you can contact Cathy Kneeland at kreel001@umn.edu. This encapsulation device trial is for those with T1D experiencing hypoglycemia unawareness.

If you have any further questions please contact me, Debbie Evans, (cell) 612-810-1933 or at debbieaevans1@gmail.com.