In 2001 and 2003, researchers at Massachusetts General Hospital (MGH) demonstrated the efficacy of a protocol to reverse of type 1 diabetes in diabetic mice. Three studies from other institutions published in the March 24, 2006 issue of Science confirmed that the MGH-developed protocol can reverse the underlying disease but were inconclusive on the role of spleen cells in the recovery of insulin-producing pancreatic islets. The new data from a study performed at the National Institutes of Health (NIH), published as a technical comment, provides additional confirmation of the ability to reverse type 1 diabetes and on the role of the spleen cells in islet regeneration.
"This data from the NIH and the earlier studies have added significantly to the understanding of how diabetes may be reversed," says Denise Faustman, MD, PhD, director of the Immunobiology Laboratory at Massachusetts General Hospital, primary author of the 2001 and 2003 studies and co-corresponding author of the current report. "It is still early, but it appears that there are multiple potential sources for regenerating islets. As a research community we should pursue all avenues. We're excited to see what will happen in humans."
In the 2001 and 2003 studies, Faustman and colleagues treated end-stage nonobese diabetic (NOD) mice with Freund's complete adjuvant, a substance that suppresses the activity of the immune cells that destroy islets in type 1 diabetes. They also introduced donor spleen cells to retrain the immune system not to attack islets and found that the protocol not only halted the immune destruction caused by diabetes but also allowed the insulin-producing pancreatic islet cells to regenerate. Evidence indicated that the sple en cells were the source of at least some of the regenerated islet cell and hastened the restoration of blood sugar levels.
The direct contribution of spleen cells to islet recovery, first described in the 2003 study, is confirmed in the current work. NIH researchers used cell lineage tracking in the form of Y-chromosomal fluorescence in situ hybridization (FISH), in combination with insulin staining, to follow the fate of male spleen cells transplanted into female recipients. The female mice that received male donor cells consistently showed Y-chromosome-positive insulin-producing islet cells, indicating that the introduced spleen cells contribute to islet recovery. The current study also showed that the degree of spleen cell contribution is influenced by mouse age at the start of treatment. Spleen cells appear to contribute to islet recovery more in mice who are older and with more advanced diabetes compared with younger mice with less advanced diabetes, in which regeneration of remaining islets may be the dominant mechanism.