A 25-year-old woman with Type 1 Diabetes (T1D) started producing her own insulin less than three (3) months after receiving a transplant of reprogrammed stem cells. She is the first person with the disease to be treated using cells that were extracted from her own body. “I can eat sugar now,” said the woman, who lives in Tianjin, China, on a call with Nature. It has been more than a year since the transplant, and, she says, “I enjoy eating everything — especially hotpot.” 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’ve completely reversed diabetes in the patient, who was requiring substantial amounts of insulin beforehand.”
The study, published in Cell today, follows results from a separate group in Shanghai, China, who reported in April that they had successfully transplanted insulin-producing islets into the liver of a 59-year-old man with Type 2 Diabetes (T2D). The islets were also derived from reprogrammed stem cells taken from the man’s own body, and he has since stopped taking insulin.
The studies are among a handful of pioneering trials using stem cells to treat diabetes, which affects close to half a billion people worldwide. Most of them have T2D, in which the body does not produce enough insulin or its ability to use the hormone diminishes. In T1D, the immune system attacks islet cells in the pancreas.
Islet transplants can treat the disease; however, there are not enough donors to meet the growing demand, and recipients must use immune-suppressing drugs 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 the laboratory, which means they potentially offer a limitless source of pancreatic tissue. By using tissue made from a person’s own cells, researchers also hope to avoid the need for immunosuppressants.
Reprogrammed cells
In the first trial of its kind, Deng Hongkui, a Cell Biologist at Peking University in Beijing, and his colleagues extracted cells from three (3) people with T1D and reverted them into a pluripotent state, from which they could be molded into any cell type in the body. This reprogramming technique was first developed by Shinya Yamanaka at Kyoto University in Japan almost two (2) decades ago. However, Deng and his colleagues modified the technique: instead of introducing proteins that trigger gene expression, as Yamanaka had done, they exposed the cells to small molecules. This offered 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 that lasted less than half an hour, they injected the equivalent of roughly 1.5 million islets into the woman’s abdominal muscles — a new site for islet transplants. Most islet transplants are injected into the liver, where the cells cannot be observed. However, by placing them in the abdomen, the researchers could monitor the cells using magnetic resonance imaging, and potentially remove them if needed.
Insulin free
Two-and-a-half (2.5) months later, the woman was producing enough insulin to live without needing top-ups, and she has sustained that level of production for more than a year. By that time, the woman had stopped experiencing the dangerous spikes and drops in blood glucose levels, which remained within a target range for more than 98% of the day. “That’s remarkable,” says Daisuke Yabe, a Diabetes Researcher at Kyoto University. “If this is applicable to other patients, it’s going to be wonderful.”
The results are intriguing; however, they need to be replicated in more people, says Jay Skyler, an Endocrinologist at the University of Miami, Florida, who studies T1D. Skyler also wants to see that the woman’s cells continue to produce insulin for up to five (5) years, before considering her ‘cured’.
Deng says the results for the other two participants are “also very positive”, and they reached the one-year mark in November 2024, after which he hopes to expand the trial to another 10 or 20 individuals. Because the woman was already receiving immunosuppressants for a previous liver transplant, the researchers could not assess whether the iPS cells reduced the risk of rejection of the graft.
Even if the body does not reject the transplant because it does not consider the cells to be ‘foreign’, in people with T1D, because they have an autoimmune condition, there is still a risk that the body could attack the islets. Deng says they did not see this in the woman because she was taking immunosuppressants; however, they are trying to develop cells that can evade this autoimmune response.
Donor cells
Transplants using the recipient’s own cells have advantages; however, the procedures are difficult to scale up and commercialize, say researchers. Several groups have started trials of islet cells created using donor stem cells.
Preliminary results for one (1) trial, led by Vertex Pharmaceuticals in Boston, Massachusetts, were reported in June 2024. A dozen participants with T1D received islets derived from donated embryonic stem cells that were injected into the liver. They were all treated with immunosuppressants. Three (3) months after the transplant, all the participants began producing insulin when glucose was present in the bloodstream. Some had become insulin independent.
In 2023, 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 T1D, who did not receive immunosuppressants. “That trial is ongoing,” says Shapiro, who is involved in running the study, which aims to enroll 17 individuals.
Yabe is also about to start a trial using islet cells produced using donor iPS cells. He plans to develop sheets of islets and surgically place them in the abdominal tissue of three (3) people with T1D, who will receive immunosuppressants. The first participant should receive their transplant early in 2025.
REFERENCE: Nature; 26 SEP 2024; Smriti Mallapaty