Researchers have used injections of patients' own stem cells to reverse the course of type 1 diabetes, reports a research team from the University of São Paulo in Brazil and Northwestern University in Chicago.
The findings, published in the current issue of the Journal of the American Medical Association, exemplify the remarkable gains made by diabetes researchers, who are battling a continuously spreading disease that now affects nearly 8% of adults and children. (See the top 10 medical breakthroughs of 2008.)
The research team, led by Dr. Julio Voltarelli of the University of Sao Paulo, is the first to successfully treat type 1 diabetes patients with their own stem cells. The group first reported its initial achievement in 2007, with 15 type 1 diabetes patients who received their own stem cells and no longer needed insulin to control their blood sugar levels. In the new study, a follow-up of their previous work, Voltarelli and his colleagues detailed the same success with an additional eight patients, and also confirmed that in the majority of them, the stem cell transplant led to an appreciable repopulation of functioning insulin-producing beta cells in the pancreas.
"I wouldn't use the word cure," says Dr. Richard Burt, one of the co-authors from Northwestern University. "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."
The idea behind the transplant is simple. In type I diabetes, the patient's own immune system turns on the beta cells that produce insulin, the hormone that breaks down the glucose we eat in food. Eventually, the immune cells will virtually eliminate all of the body's beta cells, and glucose levels will start to climb. Researchers believe that the trigger for this attack lies somewhere within the immune cells, so one possible treatment for the disease may be to wipe out the entire existing immune system and replace it with a fresh one, derived from stem cells without this destructive trait. (See pictures from an X-Ray studio.)
That's the strategy that Voltarelli's team tested. First, they carefully extracted a population of immune stem cells from the bone marrow of each diabetes patient. Then each person was treated with radiation, similar to the regimen that cancer patients receive, in order to destroy the immune system. Afterward, each patient received his own stem cells back by injection. The scientists traced blood levels of a protein, C-peptide, that beta cells produce, in order to confirm that whatever remaining beta cells the patient had were now able to grow again and repopulate the pancreas and produce insulin. Sure enough, levels of C-peptide rose in 20 of the 23 patients; 12 were able to stay off insulin therapy for three years, and eight needed only intermittent help from insulin treatments during the five-year study period. On average, the patients remained free of insulin injections for 31 months.
That's a milestone in diabetes treatment. Type I diabetes patients are locked in a constant struggle to maintain their body's insulin levels. Since their beta cells no longer produce the hormone on their own, patients must supply it themselves with multiple injections throughout the day and night, or using an insulin pump that dispenses insulin automatically through a permanent tube under the skin. Voltarelli's stem cell strategy provides a life-changing alternative that would take the burden off the patient and put it back where it belongs, on the beta cells.
That's the theory. But some experts point out that, in practice, stem cell transplants are not always a home run. For one, transplantation is a grueling and toxic process in which a portion of the body's tissues the immune system is destroyed with dangerous radiation. Then, there is the question of timing. In most cases, patients with type 1 diabetes do not show symptoms of their disease such as high blood sugar levels until they have depleted their beta cell population considerably. Dr. David Nathan, director of the diabetes center at Massachusetts General Hospital, notes that at this point, there may not be enough beta cells remaining to seed a new population of insulin-growing cells, even with an infusion of stem cells to give them a more hospitable environment. "This study shows that it can work, but how long it will work is a question," he says. Previous studies have shown that after an immune cell transplant, beta cells vigorously produce insulin for about six months, and then start to die off, victims of the same immune attack that destroyed their predecessors.
Voltarelli's team, however, has managed to show that the stem cells can give long-lasting beta cells a chance to grow at least ones that can produce insulin for about three years. Other researchers are pursuing intriguing 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," says 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." It is, as Burt says, a start.