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Injected Spleen Cells Reverse Type 1 in Mice

| Mar 1, 2004

In November 2003 the news was everywhere. “Juvenile diabetes cured in lab mice!” proclaimed the November 14, 2003, edition of The Boston Globe.

“Breakthrough sparks diabetes hope,” the BBC announced.

A discovery by a team led by Denise Faustman, MD, PhD, of the Massachusetts General Hospital in Charlestown, Massachusetts, raised the hopes of type 1s and their families everywhere. In her laboratory, Faustman injected live spleen cells from healthy nondiabetic mice into mice with type 1. The spleen cells were then turned into insulin-producing islets, completely and permanently reversing type 1 in the mice—even in those close to death.

The discovery was a surprise to the researchers themselves, who had been attempting to address the autoimmunity problem of diabetes. They were amazed to find that the pancreas spontaneously regenerated itself once autoimmunity was resolved.

"We had not only reversed autoimmunity, but had regenerated islets in the pancreas,” Faustman says. “It was a surprise to find that the pancreas had immense regenerative potential. We didn’t think we were doing that!” The results of the study were published in the November 14, 2003, issue of Science.

We’ve Heard It All Before

The cure for type 1 diabetes has been on the horizon for decades, right?

Pancreas transplants, islet transplants and drugs that prevent or slow the progression of beta cell destruction appear in the headlines regularly.

But the new therapies never seem to reach the general public.

Even the much-celebrated Edmonton Protocol of 2000 has been showing signs of failure lately, as several participants have gone back to insulin therapy.

But Faustman says her discovery is different. Other attempts at cures, she points out, don’t address the true underlying problem of type 1 diabetes-they merely address the symptoms.

“When you replace beta cells or transplant a pancreas, the autoimmunity does not go away. We decided that autoimmunity was the big bad thing that we had to deal with. We had to work at reversing established autoimmunity.”

Mice Actually Had Type 1 All Along

In order to deal with the underlying autoimmunity, Faustman’s team used mice that actually developed type 1 through an autoimmune malfunction.

“Most mouse experiments done in the past were done on mice that were not spontaneously diabetic or were very early in their disease prior to hyperglycemia, and thus the issues of recurrent disease are hard to adequately evaluate. Those mice did not have an autoimmune problem.”

Faustman and her team injected healthy donor spleen cells to train new immune cells not to attack the insulin-producing islets and expected to transplant donor islet cells once the “re-education” had occurred.

However, they were surprised to find that healthy islets spontaneously reappeared. The spleen cells migrated to the pancreases of the mice, apparently prompting regeneration of the beta cells, returning the pancreas into a healthy insulinmaking organ and ending diabetes.

Detractors Come Out of the Woodwork

Other experts, however, remain wary of this or any other “breakthrough” that promises a cure while still in early stages of study.

“I know that patients are desperate for a cure,” says Fred Levine, MD, a researcher at the University of California San Diego Cancer Center who works in the area of human beta cell growth and differentiation, “but it is very difficult. This is an early finding that deserves to be pursued, but should be regarded cautiously.”

Levine points out that other supposedly exciting cures turned out to be false hopes.

“A whole host of papers claimed to show that embryonic stem cells could be differentiated into stem cells,” he says. “Many of those papers have suffered from an experimental flaw, and it turned out that embryonic stem cells did not become stem cells.”

Mehboob Hussain, MD, of the Department of Medicine and Pharmacology at the New York University School of Medicine, earlier this year published a paper showing that islets could be regenerated using bone marrow (see “A New Islet Source on the Horizon,” May 2003 Diabetes Health). Hussain expressed both hope and restraint in his assessment of Faustman’s findings.

“It is an important finding if it can be corroborated,” he says. “It’s like a double whammy, if through one single manipulation both problems can be resolved. That there is a way of getting the immune system into a situation so that it doesn’t attack islet or beta cells, and at the same time, the [manipulation] can lead to regeneration of beta cells-that’s a really big step forward.”

Hussain advises, however, that we need to be careful when interpreting Faustman’s results.

“In general, we know that mice are not men,” he says. “Findings in the mouse might not be translatable to humans….Personally, I am on the pessimistic side, and I think it will take at least a decade before a cure for type 1 is developed. There is lots of work to be done.”

Camillo Ricordi, MD, scientific director and chief academic officer of the Diabetes Research Institute at the University of Miami School of Medicine, also expressed reservations about the study.

“There have been many studies in which autoimmunity has been prevented or reversed in… mice, and time will tell whether this is a new breakthrough or if it will be filed in the curiosity section,” he says.

Correct Autoimmunity and Diabetes Will Reverse Itself

Faustman, on the other hand, remains extremely optimistic-and not just for curing diabetes, but for curing all autoimmune disorders.

“Potentially you could just reverse the autoimmune disease, and the disease will automatically reverse itself,” she says. “Even in mice that had no islet cells, regeneration occurred. You don’t need an islet transplant! We think we have a fundamental understanding of some of these pathways that cause disease. Probably they will have broad applicability to all autoimmune illnesses.”

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Categories: Diabetes, Diabetes, Insulin, The Cure, Type 1 Issues, Type 1 Issues


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