A woman with type 1 diabetes started producing insulin (blue) after a stem cell transplant.Credit: Lennart Nilsson, Boehringer Ingelheim International GmbH, TT/Science Photo Library
A 25-year-old woman with type 1 diabetes began producing her own insulin less than three months after receiving a transplant of reprogrammed stem cells. She is the first patient to be treated for this disease using cells extracted from her own body.
“I can now eat sugar,” a woman in Tianjin told Nature over the phone. More than a year after her transplant, she said, “I like to eat everything, especially hot pot.” The woman requested anonymity to protect her privacy.
James Shapiro, a transplant surgeon and researcher at the University of Alberta in Edmonton, Canada, said the results were surprising. “They completely reversed diabetes in patients who had previously required large amounts of insulin.”
The study, published today in the journal Cell, follows the results of another 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. There are 2. The islands are 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 trials using stem cells to treat diabetes, which affects nearly 500 million people worldwide. Most of them have type 2 diabetes, where the body doesn’t produce enough insulin or has a reduced ability to use the hormone. In type 1 diabetes, the immune system attacks the islet cells of the pancreas.
Pancreatic islet transplants can treat the disease, but there are not enough donors to meet the growing demand, so recipients must use immunosuppressive drugs to prevent their bodies from rejecting the donor tissue.
Stem cells can be used to grow any tissue in the body and can be cultured in the laboratory indefinitely. This means that stem cells have the potential to provide an endless 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 attempt of its kind, cell biologist Deng Hongkui of Peking University in Beijing and his colleagues extracted cells from three type 1 diabetic patients, returned them to a pluripotent state, and from there It can now be molded into a cell shape. In your body. This reprogramming technique was first developed about 20 years ago by Shinya Yamanaka at Kyoto University in Japan. However, Deng and his colleagues modified this technique. Instead of introducing a protein that causes gene expression, as Yamanaka did, they exposed the cells to small molecules. This gives you more control over the process.
The researchers then used 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, the equivalent of about 1.5 million pancreatic islets were injected into a woman’s abdominal muscles, the new site for islet transplantation, in a surgery that took less than 30 minutes. Most islet transplants are injected into the liver, where no cells are observed. But by placing them in the abdomen, researchers could use magnetic resonance imaging to monitor the cells and potentially remove them if necessary.
insulin free
After two and a half months, the woman was producing enough insulin to survive without needing supplements, and has maintained that production level for more than a year. By that time, the woman no longer experienced dangerous spikes or drops in her blood sugar levels, and her blood sugar levels remained within her target range for more than 98 percent of the day. “That’s surprising,” says Daisuke Yabe, a diabetes researcher at Kyoto University. “It would be great if this could be applied to other patients.”
Jay Schuyler, an endocrinologist at the University of Miami in Florida who studies type 1 diabetes, said the results are interesting but need to be replicated in more people. Schuyler also wants to see if the woman’s cells continue to produce insulin for up to five years before calling her “cured.”
Mr Deng said the results for the other two participants were also “very good” and they were on track to reach the one-year mark in November, after which they hoped to expand the trial to another 10 or 20 people. There is.
Because the woman was already receiving immunosuppressive drugs from a previous liver transplant, researchers were unable to assess whether iPS cells reduced the risk of graft rejection.
Even if the body does not see the cells as “foreign” and therefore does not reject the transplant, people with type 1 diabetes are still at risk of their body attacking the islets because they have an autoimmune disease. . Professor Deng said the woman did not have these symptoms due to immunosuppressive drugs, but they are trying to develop cells that can circumvent this autoimmune response.
donor cells
Researchers say transplants using the recipient’s own cells have advantages, but the procedure is difficult to commercialize on a large scale. Several groups have begun testing islet cells produced using donor stem cells.
Preliminary results from a trial led by Vertex Pharmaceuticals of Boston, Massachusetts, were reported in June. Twelve participants with type 1 diabetes had pancreatic islets derived from donated embryonic stem cells injected into their livers. They were all treated with immunosuppressants. Three months after transplantation, all participants began producing insulin when glucose was present in their bloodstream4. Some people were no longer dependent on insulin.
Last year, Vertex began another trial in which islet cells derived from donated stem cells were placed in a device designed to protect them from attack by the immune system. It was transplanted into a type 1 diabetic patient who was not receiving immunosuppressants. “That trial is ongoing,” said Shapiro, who is participating in the study, which aims to enroll 17 people.
Dr. Yabe is also planning to begin clinical trials using pancreatic islet cells created from donor iPS cells. He will create sheets of pancreatic islets and surgically place them into the abdominal tissue of three type 1 diabetic patients who will receive immunosuppressive drugs. The first participants will need to undergo transplants early next year.
