Encellin is working to eliminate insulin injections for diabetic patients with an insulin-producing implant containing live cells.November 27, 2017
A California startup hopes to eliminate insulin injections for diabetic patients with an insulin-producing implant containing live cells. The device is in preclinical trials and the company, Encellin, is preparing for clinical trials. The concept of packaging cells in semipermeable membranes could have other medical uses as well.
Cells naturally produce small molecules, proteins, and hormones to keep a body functioning properly, Encellin CEO and co-founder Crystal Nyitray, who pioneered the technology, explained. Rather than relying on injections or pills to replace biomolecules not produced by diseased cells, she envisions medical treatments using encapsulated cells.
“Cells are the ultimate smart machines,” Nyitray said. “The packages can hold molecular machines that secrete the necessary treatment.”
About 20 million people worldwide have type-1 diabetes, which leaves them dependent on insulin injections to help regulate their blood sugar. The disease occurs when patients’ immune systems kills cells in the pancreas that produce the hormone insulin, which enables glucose, a form of sugar, to enter their cells.
To replace the missing insulin, patients with type-1 diabetes inject themselves with insulin around mealtime. This helps their bodies utilize the surge of glucose that enters their bloodstream as they digest their food.
Despite frequent monitoring of blood sugar levels and dose adjustments, insulin injections do not perfectly recreate the natural waves of insulin released from the pancreas. This leaves patients constantly working to avoid chronically high or low blood sugar, which can cause blindness, diabetic coma, or life-threatening insulin shock.
An effective way of providing patients with tighter control over their glucose levels is with a transplant of clusters of insulin-producing cells, called islets. Several research groups have been working on this technology with mixed results.
All seven patients in a clinical trial of islet transplantation at the University of Alberta and 44% of patients in another trial at medical centers in North America and Europe needed no insulin injections for a year. Still, transplant recipients had to take immunosuppressive drugs for the rest of their lives to prevent their immune systems from attacking the transplanted cells.
San Francisco-based Encellin wants to extend the lifetime of transplanted islets. To do this, it surrounds the cells with a thin, porous membrane, creating a flexible package about the size of a quarter. The membrane protects the cells from attack by a patient’s immune system, while keeping the cells bathed in an environment they need to survive.
The design of the encapsulated cells grows out of Nyitray’s research while earning her Ph.D. in the lab of Tejal Desai at the University of California, San Francisco. In work published in 2015, Nyitray and her colleagues packaged cells in a membrane of polycaprolactone about 10 µm thick, containing pores ranging from 30-100 nm.
The pores were just large enough to allow nutrients, oxygen, and glucose to pass through and reach the encapsulated cells. The islet cells respond to glucose levels in the blood by producing insulin, which seeps out of the package and into the bloodstream, producing a more natural wave of insulin release. The pores also slowed the diffusion of antibodies and cytokines, inflammation-causing molecules that induce cell death, into the package.
When implanted in mice, the package kept mouse cells that model islet cells alive for 90 days. This year, the Desai lab encapsulated human stem cells, and kept them healthy for six months when implanted in diabetic mice.
Encellin built on Nyitray’s original work, encapsulating donated human islet cells inside a proprietary polymer whose membranes are about as thin as a human hair. When designing the implant, the company looks beyond the composition of the porous membrane and also considers ways to make the package “a happy home for cells,” Nyitray said.
Encellin is not the only company looking to encapsulate living cells. ViaCyte started testing its cell-based implants for diabetes in clinical trials earlier this year. ViaCyte’s implant contains stem cells that mature into pancreatic cells once inside a patient.
The concept of encapsulating cells to restore biological functions lost to disease could potentially apply to more medical conditions than diabetes alone. Implants containing pituitary cells could balance hormones involved in growth and fertility in patients with underactive pituitary glands. Stem cell implants could stimulate heart cells to repair themselves after a heart attack or prevent neuronal degeneration in patients with Parkinson’s disease. Another potential treatment involves encapsulating and implanting cells engineered to secrete a protein that curbs growth of cancer cells.
“Diabetes is just the beginning,” Nyitray said. “I do believe this will completely change how we think about therapies.”
Melissae Fellet is a science writer based in Missoula, MT.
Read more about Cell Therapy on AABME.org.