Many people with diabetes prick their fingers several times a day to measure blood sugar levels and decide on the insulin doses they need. Implants of pancreatic cells that normally make insulin in the body— so-called islet cells—can render this cumbersome process unnecessary. Likewise, cellular implants could transform treatment of other disorders, including cancer, heart failure, hemophilia, glaucoma and Parkinson’s disease. But cellular implants have a major drawback: recipients must take immunosuppressants indefinitely to prevent rejection by the immune system. Such drugs can lead to serious side effects, including an increased risk of infection or malignancies.
Over several decades scientists have invented ways to enclose cells in semipermeable protective membranes that keep the immune system from attacking the implanted cells. These capsules still allow nutrients and other small molecules to flow in and needed hormones or other therapeutic proteins to flow out. Yet keeping the cells out of harm’s way is not enough: if the immune system views the protective material itself as foreign, it will cause scar tissue to grow over the capsules. This “fibrosis” will prevent nutrients from reaching the cells, thereby killing them.
Now investigators are beginning to solve the fibrosis challenge. For instance, in 2016 a team at the Massachusetts Institute of Technology published a way to make implants invisible to the immune system. After producing and screening hundreds of materials, the researchers settled on a chemically altered version of a gel called alginate, which has a long history of safe use in the body. When they implanted islet cells encapsulated in this gel into diabetic mice, the cells immediately produced insulin in response to changing blood sugar levels—keeping them under control over the course of a six-month study. No fibrosis was observed. In separate work, the team later reported that blocking a particular molecule (the colony-stimulating factor 1 receptor) on macrophages, which are immune cells important in fibrosis, can inhibit scarring. Adding such a blocker should further enhance the survival of implants.
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Several companies have formed to develop encapsulated-cell therapies. One of these, Sigilon Therapeutics, is advancing the technology developed at M.I.T. to design treatments for diabetes, hemophilia and a metabolic disorder called lysosomal storage disease. Pharmaceutical company Eli Lilly is partnering with Sigilon on the diabetes work. In other examples, Semma Therapeutics is also focusing on diabetes, using its own technology; Neurotech Pharmaceuticals has implants in clinical trials for glaucoma and various eye disorders marked by degeneration of the retina; Living Cell Technologies is running clinical trials of implants for Parkinson’s and is developing therapies for other neurodegenerative conditions.
Today the cells being incorporated into capsules are drawn from animals or human cadavers or are derived from human stem cells. One day implantable cell therapies may include a broader array of cell types, including some engineered through synthetic biology—which reprograms a cell’s genetics to make it perform novel functions, such as controlled, on-demand release of specified drug molecules into a tissue. These are still early days. Neither the safety nor the efficacy of encapsulated-cell therapy has been proved in large clinical trials, but the signs are encouraging.