A local IL-10 “shield” prolonged the function of transplanted islets in mice and was tested in primates
In mice, transplanted insulin-producing islets maintained normal blood glucose for 100 days when placed beside capsules that released IL-10
On 5 August, a Rice University team described cell-containing capsules that continuously release IL-10 near transplanted human islets in a Science Advances article. In diabetic mice, these neighboring capsules helped the islets maintain blood glucose within the normal range for up to 100 days. In a month-long pilot study involving two healthy cynomolgus macaques, the authors tested whether IL-10 remained present around the capsules in a primate.
Pancreatic islets produce insulin. In this study, the researchers placed them inside permeable alginate capsules made from a gel-like material. The body reacts to foreign material. Immune cells first gather around the capsule, and fibroblasts then form a collagen layer around it. This layer impairs the exchange of substances between the islets and the surrounding tissue, causing the islets to gradually lose function.
The authors assigned two tasks to different cell types. The islets produced insulin, while neighboring capsules contained retinal pigment epithelial cells, which normally form a cell layer at the back of the eye. The researchers genetically modified these cells to release IL-10 continuously. This protein reduces the local inflammatory response around the implant.
In the experiment with diabetic mice, each group received 2 000 human islet equivalents, which are standard units for measuring the amount of islet tissue. Each group contained six animals. Islets without protective cells and islets placed beside unmodified retinal pigment epithelial cells stopped maintaining normal blood glucose before the third week. In the group with IL-10-producing cells, the islets maintained normal blood glucose for 100 days, which was 4,76 times longer than islets without protection. On day 100, the researchers found more viable islets and more human C-peptide in the blood of mice in this group, as well as less fibrous tissue on the capsules.
In a separate experiment in healthy mice, single-cell analysis on the seventh day indicated how this effect may have developed. IL-10 altered the activity of monocytes and macrophages, which are immune cells involved in inflammation around the implant. Their inflammatory program weakened, and genes associated with recognizing foreign material and triggering rejection became less active. After several weeks, less fibrous tissue remained around the capsules. In the diabetic model, islets placed near IL-10 retained their function for longer.
The month-long primate pilot included one healthy macaque that received IL-10-producing capsules and one control macaque that received the same cells without the genetic modification for protein production. After one month, IL-10 was detected in the abdominal fluid of the macaque that received the IL-10-producing capsules. The authors demonstrated the ability of transplanted human islets to maintain normal blood glucose in mice with diabetes.
Cell replacement must accomplish two tasks: provide the body with the required cells and preserve the conditions those cells need to function after transplantation. In this design, the islets regulate blood glucose, while neighboring cells reduce inflammation around them. Separate capsules protect the implant, while the islets remain the source of insulin.