For the 1.25 million Americans with type 1 diabetes, daily insulin shots and blood-sugar checks are an inconvenient reality that can’t be skipped—the routine keeps them alive and healthy.
The reason they need it: Their own insulin-producing islet cells, located in the pancreas, aren’t working. Now, scientists across the US are racing to develop effective ways to transplant new islet cells in people with diabetes—an alternative that could make daily life easier and lower risk for insulin side effects like dangerous low blood sugar episodes.
Among the researchers, one young California bioengineer’s work is gaining attention and winning awards.
“The cell is the original smart machine,” notes Crystal Nyitray, PhD, on the website of Encellin, the biotech start-up she founded in 2016. “All drugs, devices, and even digital health approaches are trying to restore or copy these functions. At Encellin, we believe in the human cell and creating a safe and reliable solution for patients. We are creating a technology to promote cell function and protection.”
Dr. Nyitray established Encellin soon after she received her PhD in chemistry and chemical biology from the University of California San Francisco in 2015. Her work at UCSF, with advisor Tejal Desai, PhD, chair of the Department of Bioengineering and Therapeutic Sciences in UCSF’s schools of Pharmacy and Medicine, focused on developing a packaging system for islet cells.
The system had to multi-task in many ways. It had to give the cells access to oxygen and nutrients, let them keep tabs on glucose levels in the bloodstream and let them pump it into the bloodstream as needed. But that’s not all. The package also had to protect the transplanted cells from attacks by the body’s own immune system.
Lab studies show that Encellin’s “ultra thin-film implantable cell delivery system” keeps islet cells alive and functioning. In a 2015 study in the journal ACS Nano, Dr. Nyitray and others found that cells in the packaging survived for 90 days in lab animals. New blood vessels grew around the transplants and the cells produced insulin in response to rising glucose levels. In a 2016 study from Dr. Desai’s lab, also published in ACS Nano, human islet cells packaged in the tiny film envelopes survived for six months in mice—and the cells made and released insulin in response to rising blood glucose levels.
“Our technology is built on allowing the cell to maintain its normal function,” Dr. Nyitray noted in a 2017 interview. “In the instance of diabetes, our investigational therapy is being developed to detect glucose and secrete insulin through the membrane, and at the same time protect those enclosed cells,”
In both studies, the packaging prevented the implanted cells from triggering an immune-system reaction. That’s important because this protection could pave the way for the development of an islet-cell transplant system in people that won’t require them to take immune-suppressing anti-rejection drugs for the rest of their life.
Currently, people with diabetes who receive a transplanted pancreas (typically not possible unless you are also having a kidney transplant) or who receive islet-cell transplants as part of a research study in the US must take these drugs so that their own body won’t attack the new cells. The drugs work, but raise risk for bacterial and viral infections as well as for mouth sores, nausea, diarrhea, high cholesterol, high blood pressure, fatigue and even some cancers.
Dr. Nyitray’s ultimate goal? “Our proprietary technology will be loaded with glucose-responsive insulin-secreting cells, and implanted under the skin,” she notes online. “Once inside the device cells will be protected from the immune system but still able to maintain nutrient exchange to respond to their environment.”
The technology Nyitray’s company is exploring was first developed in Desai’s Therapeutic Microtechnology and Nanotechnology Laboratory at UCSF. The device’s whisper-thin film—it’s only as thick as the diameter of a human hair, according to the Alliance of Advanced Biomedical Engineering—is made of polycaprolactone (PCL).
This medical-grade polyester is currently used in teeth guards that kids and adults wear at night, in tiny tubes used to guide the growth of damaged nerve fibers and in surgical sutures. Researchers are also looking at PCL’s potential as an implant to deliver medications directly to the eyes and to tumors and as a scaffold for growing human tissue. PCL may be an ideal package for islet cells, the studies note, because it can be used to create thin, flexible membranes with pores that let in glucose and nutrients, let out insulin and exclude bigger immune-system molecules.
Encellin’s ultra thin-film device won a $10,000 research prize in The American Diabetes Association's 22nd Annual Leaders Forum HealthTech Showcase in Northern California in late 2017. The company also won a 2016 Innovation Award from the San Francisco-based Rosenman Institute, an organization that aims to support the development of innovative medical-device technologies.
“I am extremely pleased to see that technology developed in Tejal Desai’s group is getting to the point that we can explore this for therapeutic purposes,” Matthias Hebrok, PhD, the director of the Diabetes Center at UCSF and a member of Encellin’s scientific advisory board, noted on the UCSF website. “Encapsulation and protection of islet cells remain a critical hurdle that needs to be overcome before cell therapy becomes a reality in type 1 diabetes.”
The device may have wider application, to help treat other health conditions where implanting healthy cells can play a role. “Diabetes is just the beginning,” Nyitray told a recent gathering of biomedical engineers. “I do believe this will completely change how we think about therapies.”