Implants containing specially wrapped insulin-producing cells derived from embryonic stem cells can regulate blood sugar in mice for several months, according to research presented this month at the International Society for Stem Cell Research conference in San Francisco. San Diego-based ViaCyte (formerly Novocell), which is developing the implant as a treatment for type 1 diabetes, is now beginning the safety testing required for approval from the U.S. Food and Drug Administration before human testing can start.
“It’s still a long road toward a treatment for diabetes, but in my mind they have made astonishing progress,” says Gordon Weir, head of Islet Transplantation and Cell Biology at Joslin Diabetes Center, in Boston. But he cautions that taking the next step is likely to be tricky. The technology “tends to work well in rodents, but moving it to larger animals gets more complicated,” says Weir, who is not involved with the company. “You need more cells, and we’re guessing the immune system [reaction] is more complex.”
In type 1 diabetes, the immune system attacks the insulin-producing beta cells of the pancreas, forcing patients to rely on injections of the hormone to regulate blood sugar. Transplants of pancreatic cells from cadavers to human patients have shown that this type of cell therapy can free type 1 diabetics from daily insulin injections. But the scarcity and variable quality of this tissue makes it an impractical therapy. For the last two decades, scientists have searched for alternative sources of cells, focusing in large part on cells from the pancreas of fetal or neonatal pigs. ViaCyte, which began its efforts more than 10 years ago, has focused on embryonic stem cells.
The research exemplifies the challenges of creating cell replacement therapies from embryonic stem cells. No such treatments yet exist and only one company has won FDA approval to begin human testing. That effort was put on hold last year due to safety concerns.
After years of research, ViaCyte developed a recipe capable of transforming embryonic stem cells into immature pancreatic cells, called progenitors. The recipe is a combination of three small molecules and five proteins, and it attempts to replicate what cells would experience in the developing embryo.
But scientists haven’t yet been able to create fully “differentiated” beta cells in a dish. This is important because undifferentiated cells carry risk of turning cancerous. In a paper published in 2008, the company showed that transplanting the pancreatic progenitors into mice pushed these cells to fully differentiate inside the animal, enabling them to regulate blood sugar.
However, in some cases, the cells formed clumps of cancerous tissue called teratomas, a major safety concern with stem cell therapies. So in the new experiments, the scientists encased the cells in tea-bag like membrane. “Encapsulation protects cells from getting killed by the immune system and would contain teratoma cells,” says Weir. Encapsulation also allows the cells to be removed, if needed, says Kevin D’Amour, a principal scientist at Viacyte who presented the research.