In a First, Woman’s Type 1 Diabetes Reversed by a Stem Cell Transplant

The 25-year-old woman had suffered through decades of medical nightmares.

A native of Tianjin, a city roughly two hours west of Beijing, she was diagnosed with Type 1 diabetes 11 years ago. A chronic autoimmune disease, her body’s immune system savagely attacks the cells in her pancreas that produce insulin, spiking blood sugar to deadly levels—even after a few nibbles of rice.

Following two liver transplants and a whole pancreas transplant, her blood sugar levels remained unstable. The new pancreas had to be removed after causing life-threatening blood clots. At the end of her rope, she signed up for a highly experimental procedure. Scientists would remove fatty cells from her body, convert them into functional insulin-producing tissues, and insert them into her belly.

In just three months, her body began producing insulin to the point she no longer relied on external insulin shots to manage blood sugar levels. The transplanted cells lasted at least one year—when the study ended—with no signs of waning efficacy and few side effects.

The transplants restored the woman’s ability to process sugar and carbohydrates to that of non-diabetic people, according to a measure for long-term blood sugar stability. In a sense, it reversed her condition completely.

“I can eat sugar now…I enjoy eating everything, especially hotpot,” she told Nature.

Induced pluripotent stem cells, which transform mature cells into a stem cell-like state, are at the heart of the study. Using a chemical soup, scientists can then nudge these cells to grow into different types of tissues or organs.

The study, published in Cell, is the latest effort to use the technology to tackle diabetes.

“They’ve completely reversed diabetes in the patient, who was requiring substantial amounts of insulin beforehand,” said James Shapiro at the University of Alberta, who was not involved in the study.

Insulin on Call

Whenever we eat a carbohydrate-heavy meal—say pasta, rice, bread—or a tasty dessert, the body breaks the carbohydrates down into sugar. These sugars swirl around the bloodstream and cause the pancreas to release insulin, a hormone that helps the sugars enter cells as fuel.

In both types of diabetes, the process goes awry. Type 2 diabetes may be more familiar. Here, like a broken thermostat, cells that release insulin can no longer sense and respond to rising blood sugar levels. This type of diabetes is often managed with insulin shots.

Type 1 diabetes is more nefarious. Here, the body’s immune system attacks insulin-producing cells called islets. The disease often occurs in kids or in early adulthood, and there is no treatment. Regardless of type, chronically high blood sugar levels can severely damage eyesight, nerves, and blood vessels over time.

If broken islets are the problem, why not replace them?

Enter induced pluripotent stem cells (iPSCs). Scientists make iPSCs by transforming mature cells into stem cells, which have the ability to theoretically grow into any other type of cell. These cells have a unique advantage in that they come from the person’s own body—that is, used in transplants, they reduce the chance of rejection by the immune system.

Normally, scientists engineer iPSCs by adding genes for four specific proteins. However, this team developed a recipe to reprogram cells using a chemical bath. Compared to genetic engineering, the process offers far more control. Like cooking, it’s easier to tweak the process on demand.

They first took fatty cells from the woman, reprogrammed them into iPSCs, and transformed these into functional islet cells. As a sanity check, some of the engineered islets were tested in hundreds of mice to see if they produced insulin and to monitor any side effects.

Cancer was one worry. Reversing adult cells back into stem cells carries the risk the cells might grow out of control. The mice studies didn’t find cancer. The critters also had healthy hearts, livers, kidneys, lungs, and brains after the transplant, suggesting the approach was relatively safe.

In a simple 90-minute surgery, the team then injected the equivalent of 1.5 million islet cells into the woman’s belly muscles. The islets had been frozen, rethawed, and given a health check. Being able to freeze tissues means they might be transported between facilities and hospitals, allowing for more flexibility.

Inserting the islets into the belly was a strategical move. Previous attempts at cell therapy injected cells into the liver. This is easy enough in lab experiments but harder to monitor in clinical use. The belly is more readily examined with ultrasound and other imaging methods.

A Way Forward

Two weeks after transplantation, the woman’s daily insulin needs had fallen dramatically. Seventy-five days later she no longer depended on daily insulin shots and remained completely independent of them for at least a year. Her blood sugar levels remained within a normal range, similar to those of people without diabetes. Multiple measures of sugar metabolism improved after the treatment. The graft had few side effects and showed no signs of turning cancerous.

Most of us know someone with diabetes. While controllable with diet, exercise, and insulin injections, the condition still increases the chances of stroke, dementia, and other diseases. Personalized stem cell therapy may offer a longer-term alternative.

The current work builds on an earlier study that treated a person with Type 2 diabetes. Though the reprogrammed cells did turn into insulin-pumping cells in that study, they couldn’t generate enough insulin to keep the person’s blood sugar under control. By fine-tuning the procedure, the new study advances a long-term solution for a disease that plagues millions of people.

There are caveats. The woman was already on immunosuppressant drugs for her liver transplants. This makes it difficult to determine if the iPSC-derived transplants can trigger an immune reaction, and if so, how severe.

Also, because the strategy is highly personalized, scaling it up may prove difficult. Another approach, championed by Vertex Pharmaceuticals, uses islets derived from embryonic stem cells directly injected into the liver. Patients produced insulin within three months of the implant.

The new results are part of an ongoing clinical trial for people with both Type 1 and 2 diabetes. Launched in 2021, the trial is expected to have safety results by the end of next year.

The results here are from just one person over one year. Whether they extend to elderly people, who’ve lived with the condition longer, or those with other conditions such as high blood pressure will have to wait until the end of the trial.

Still, overall, the data show the potential of “personalized cell therapy,” wrote the team.

Image Credit: Diabetesmagazijn.nl / Unsplash