Spleen Cells Fail as Diabetes Treatment

It seemed too good to be true. And it was. Three new studies dash hopes that spleen-cell injections could help reverse type 1 diabetes.

But there's a silver lining. Or, rather, an islet-cell lining. The new studies show that the most important part of the earlier study is true. Some of the insulin-making islet cells lining the pancreas can recover.

This means that if scientists find a way to stop the haywire immune responses that destroy islet cells and cause type 1 diabetes, a patient could be freed from the need for insulin injections. No spleen cells needed.

The new studies show this can be done in mice with type 1 diabetes. And it's possible for humans, suggests Emil R. Unanue, MD, head of the departments of pathology and immunology at Washington University, St. Louis. Unanue [pronounced ew-NAN-uh-way] led one of the three new studies reported in the March 24 issue of Science.

"There is a window of time, soon after an individual loses blood-sugar control, when there is still [islet]-cell function in the pancreas," Unanue tells WebMD. "If at that time you stop the [harmful] immunologic process, you can rescue a level of insulin function that allows the individual to be free of the need for insulin therapy."

How to Cure Type 1 Diabetes

It's going to take two steps to cure type 1 diabetes. The first step is to stop the body's immune system from attacking islet cells. The second step is to get some new islet cells -- by letting surviving cells grow and multiply, by transplanting donor cells, or by encouraging stem cells to become new islet cells.

In 2003, Massachusetts General Hospital researcher Denise Faustman, MD, PhD, and colleagues apparently found a way to do this -- in mice.

They used an immune-boosting substance called CFA that drives hyperactive anti-islet immune cells to suicide. This put destructive immune responses on hold. Then they gave the mice temporary islet-cell transplants to tide them over until they could grow new islet cells. Finally, they gave the mice repeated injections of spleen cells from other mice. It seemed that these spleen cells gave rise to new islet cells.

Repeat Experiments

Unanue's team at Washington University, a team led by Louis Philipson, MD, PhD, at the University of Chicago, and a team led by Diane Mathis at Harvard's Joslin Diabetes Center all tried to repeat the Faustman experiment.

It didn't work. None of the three teams got the same result. The spleen cells, it turns out, didn't become islet cells.

That means the mice should have died once their temporary islet transplants were removed. But a few of them didn't die. Instead, their islet cells recovered and began making enough insulin to keep the animals alive.

No Cure, but a Big Step Forward

Apparently, a few islet cells (or precursor cells that can become islet cells) survive the immune attack. When the immune attack is put on pause, the cells grow and start making insulin.

"The positive thing is that, yes, the destructive immunologic process can be controlled," Unanue says. "Even when you have a fully diabetic mouse, there is still a window of time in which you can rescue [islet]-cell function."

How does Faustman feel about having a major part of her findings refuted? She's delighted.

"We are elated by these three stories coming out," Faustman tells WebMD. "These papers now show that others, too, can cure these end-stage diabetic animals. And they show the cure is sometimes totally driven by regeneration of islets in the pancreas. All three show they can do it independent of live, introduced stem cells. It is extremely good news."

'$64,000 Question'

Unanue says while the destructive immune process of type 1 diabetes can be put on hold, it's still not possible to stop it once and for all. And even if scientists leap that hurdle, it's still probable that this will rescue islet cells in people who've had type 1 diabetes for many years. They likely will need some kind of islet transplant -- or some way to encourage other precursor cells to become insulin-making cells.

That last idea isn't moonshine. For example, a recent study in Switzerland showed that human fat tissue contains cells that can become insulin-making cells.

"The $64,000 question is, if you had diabetes for 10-20 years, can you regenerate beta cells all by yourself, or do you need a boost as well?" Faustman says. "If they need a boost, we will have many cell populations available in the future. But our clinical hope is that getting rid of the disease will become possible simply by getting rid of autoimmunity."

Unanue, too, is optimistic.

"There is indeed significant progress in our understanding of how the immunologic process against [islet] cells can be controlled," he says. "It all should actually result in new ways of looking at the disease or actually formulating future therapies for it. Type 1 diabetes is a very complex chronic disease. There are many components. But the understanding is going so well, we should see new developments before too long."

By Daniel J. DeNoon, reviewed by Louise Chang, MD

SOURCES: Chong, A.S. Science, March 24, 2006; vol 311: pp 1774-1775. Nishio, J. Science,March 24, 2006; vol 311: pp 1775-1778. Suri, A. Science,March 24, 2006; vol 311: pp 1778-1780. Kodama, S. Science,March 24, 2006; vol 302: pp 1223-1227. Timper, K. Biochemical and Biophysical Research Communications, 2006; vol 341: pp 1135-1140. News release, Washington University. News release, University of Chicago. News release, Joslin Diabetes Center. Emil R. Unanue, MD, head, departments of pathology and immunology, Washington University, St. Louis. Denise Faustman, MD, PhD, Massachusetts General Hospital and Harvard University Medical School, Boston.