Stem Cell Transplant May Reverse Type 1 Diabetes

Type 1 diabetes is a lifelong disease that affects more than a million American children and adults. It occurs when the person’s own immune system attacks and destroys the insulin-producing beta cells in the pancreas. Since the cells no longer produce insulin, people with type 1 diabetes must supply it themselves. This means undergoing multiple injections throughout the day and night, or having insulin delivered by an insulin pump through a permanent tube under the skin. But scientists may have found a way to free type 1 diabetics from their constant struggle.

In a dynamic new study, Dr. Julio Voltarelli of the University of São Paulo in Brazil and colleagues from Northwestern University in Chicago were able to reverse the course of type 1 diabetes with a patient’s own stem cells. “I wouldn’t use the word cure,” said Dr. Richard Burt, one of the co-authors from Northwestern. “But it appears we changed the natural history of the disease. It’s the first therapy for patients that leaves them treatment-free—no insulin, no immune suppression for almost five years.”

Burt reported the team’s initial achievement in 2007, with 15 diabetic patients who received their own stem cells and no longer needed insulin to control their blood sugar levels. In this follow-up, they detail the same success with eight additional patients. Insulin-free time lasted more than four years for one patient, more than three years for four patients, more than two years for three patients, and at least one year for four patients. Eight had to go back to using insulin, but required lower doses than they did before the procedure.

To confirm the lasting effects of the therapy, the researchers measured the patient’s levels of C-peptides, which show how well the body is producing insulin. They found those levels increased in 20 of the 23 patients. And even the eight who relapsed still had significantly higher levels of C-peptide by 36 months. “Because late complications of diabetes on the microvascular compartment are inversely related to C-peptide levels, it is probable that even those patients who resumed insulin are at lower risk for long-term diabetes complications,” the researchers said.

The strategy behind the procedure, known as autologous non-myeloablative hematopoietic stem-cell transplantation, is simple. First, CD34 stem cell, which can grow into all white blood cells of the immune system, are extracted from the patient’s bone morrow and stored. Next, the patients receive drugs that destroy what remains of their immune system, at the same time eliminating the components of the immune system that attack the islets. Finally, the stored stem cells are returned to the patient and left to regenerate a fresh immune system that will no longer attack the islet cells.

Burt says a larger randomized trial is now planned in both Brazil and in the United States. As with the existing trial, newly-diagnosed patients will be selected but this time, some of the patients will receive placebo. Other researchers are pursuing new stem cell options, including stem cells that can be grown from a patient’s own skin, which would eliminate the need for extracting immune stem cells from bone marrow. “Every door that we open leads to another door,” said Burt. “All research is built by sitting on the shoulders of other studies. This trial is something that will contribute to and move the field of stem cell therapy forward.”

A similar procedure developed by Burt has already shown success in another autoimmune disease—multiple sclerosis. Results published in January showed that many patients benefitted through the reprogramming of their immune systems, this time to stop it from attacking nerve and brain cells.

Living with diabetes is a daily challenge. In addition to having to check their insulin levels and take injections, diabetics must also carefully balance their food intake and their exercise to regulate their blood sugar levels in an attempt to avoid hypoglycemic (low blood sugar) and hyperglycemic (high blood sugar) reactions, which can be life-threatening. Diabetes is associated with long-term complications that affect almost every part of the body. The disease often leads to blindness, heart and blood vessel disease, stroke, kidney failure, amputations, and nerve damage.

In recent years, pancreas transplants have been used to treat type 1 diabetes, but not only is the operation itself serious, the side effects of the drugs required to prevent the immune system from fighting the new organ may be worse than the problems caused by diabetes. Islet cell transplant is also being investigated and has been achieved in rodents and in experimental trials in humans. However, the function of transplanted islets is lost over time, and few recipients are able to stop using insulin for very long. They also have side effects from immunosuppressive drugs.

The new findings were reported in the April 15 issue of the Journal of the American Medical Association.