25-year-old woman with diabetes type 1 began producing his own insulin less than three months after receiving a transplant of reprogrammed stem cells. She is the first person with the disease to be treated using cells taken from her own body, nature.com reported.
“Now I can eat sugar” said the woman, who lives in the Chinese city of Tianjin. It's been more than a year since the transplant and I'm happy to eat everything. The woman asked to remain anonymous to protect her privacy.
James Shapiro, a transplant surgeon and researcher at the University of Alberta in Edmonton, Canada, says the results of the surgery are stunning. “They completely reversed the diabetes in the patient who required significant amounts of insulin before.”
The study, published in Cell, follows results from a separate group in Shanghai, China, where they reported in April that they had successfully transplanted insulin-producing "islets" in the liver of a 59-year-old man with type 2 diabetes. The islets were also derived from reprogrammed stem cells taken from the man's own body, and he has since stopped taking insulin.
These studies are among the few pioneering studies of using stem cells to treat diabetes, which affects nearly half a billion people worldwide. Most of them have type 2 diabetes, in which the body does not produce enough insulin or its ability to use the hormone decreases. In type 1 diabetes, the immune system attacks the islet cells in the pancreas.
Islet transplants can treat the disease, but there are not enough donors to meet the growing demand, and recipients must use drugs to suppress the immune system to prevent the body from rejecting the donor tissue.
Stem cells can be used to grow any tissue in the body and can be cultured indefinitely in a laboratory, meaning they potentially offer an unlimited source of pancreatic tissue. By using tissue made from a person's own cells, the researchers also hope to avoid the need for immunosuppressants.
In a first-of-its-kind trial, Deng Hongkui, a cell biologist at Peking University, and his colleagues extracted cells from three people with type 1 diabetes and returned them to a pluripotent state, from which they could be molded into any type of cell in the body. This reprogramming technique was first developed by Shinya Yamanaka at Kyoto University in Japan almost two decades ago. But Dunn and his colleagues modified the technique: Instead of introducing proteins that trigger gene expression, as Yamanaka did, they exposed the cells to small molecules. This offers more control over the process.
The researchers then used the chemically induced pluripotent stem (iPS) cells to generate 3D clusters of islets. They tested the safety and efficacy of the cells in mice and non-human primates.
In June 2023, in an operation lasting less than half an hour, they injected the equivalent of approximately 1.5 million islets into the woman's abdominal muscles — a new position for islet transplants. Most transplanted islets are injected into the liver, where the cells cannot be observed. But by placing them in the abdomen, researchers can monitor the cells using an MRI and possibly remove them if necessary.
Two and a half months later, the woman produces enough insulin to live without needing supplementation, and maintains this level of production for more than a year. By this time, the woman has stopped experiencing the dangerous spikes and dips in her blood sugar levels, which remain within the target range for more than 98% of the day. “This is remarkable” says Daisuke Yabe, a diabetes researcher at Kyoto University. “If this applies to other patients, that would be wonderful.”
The results are intriguing, but they need to be replicated in more people, says Jay Skyler, an endocrinologist at the University of Miami in Florida who studies type 1 diabetes. Skyler also wants to see if the woman's cells continue to make insulin up to five years before they consider her “cured”.
Dunn says the results for the other two participants were “also very positive” and will hit the one-year mark in November, after which he hopes to expand the trial to 10 or 20 more patients.
Because the woman had already received immunosuppressants for a previous liver transplant, the researchers could not assess whether the iPS cells reduced the risk of graft rejection.
Even if the body does not reject the transplant because it does not consider the cells to be “foreign”, in people with type 1 diabetes, because they have an autoimmune disease, there is still a risk that the body can attack the islets. Deng says they didn't see this in the woman because of the immunosuppressants, but they are trying to engineer cells that can avoid this autoimmune response.
Transplants using the recipient's own cells have advantages, but the procedures are difficult to scale and commercialize, researchers say. Several groups have begun trials of islet cells created using donor stem cells.
In June, preliminary results were reported from a trial led by Vertex Pharmaceuticals in Boston, Massachusetts. A dozen participants with type 1 diabetes received islets from donated embryonic stem cells that were injected into their livers. All of them were treated with immunosuppressants. Three months after the transplant, all participants began to produce insulin when glucose was present in their blood. Some had become independent of insulin.
Last year, Vertex launched another trial in which islet cells derived from donated stem cells were placed in a device designed to protect them from immune system attacks. It was transplanted into a person with type 1 diabetes who was not receiving immunosuppressants. “This process is ongoing,” says Shapiro, who participated in the study, which aims to enroll 17 people.
Yabe is also about to begin a trial using islet cells produced using donor iPS cells. He plans to develop islet sheets and surgically implant them into the abdominal tissue of three people with type 1 diabetes who will receive immunosuppressants. The first participant should receive their transplant early next year.