Spleen Cell Transplantation Reverses Autoimmune Diabetes

Diabetes researchers have found that transplantation of adult spleen cells into a mouse model for human type I diabetes resulted in suppression of autoimmune activity, return to normoglycemia, and apparent permanent reversal of the disease.

Type I diabetes is an autoimmune disorder characterized by immune cell attack on the insulin-producing islet cells of the pancreas. As islet cells die, insulin production ceases, and blood sugar levels rise, damaging organs throughout the body.

Investigators at Harvard Medical School (Boston, MA, USAedu) transplanted mature spleen cells in Freund's complete adjuvant into a line of non-obese diabetic (NOD) mice, which served as a model for human type I diabetes. They found that this treatment eliminated autoimmunity and permanently restored normoglycemia. The return of endogenous insulin secretion was accompanied by the reappearance of pancreatic beta cells.

Male spleen cells were transplanted into female mice. The investigators then found that a large proportion of new pancreatic cells contained the male Y chromosome. In another experiment, donor spleen cells were marked with a fluorescent green protein, and again donor cells were found throughout the newly developed pancreatic islets. When irradiated spleen cells, which cannot reproduce, were transplanted, the mice recovered from diabetes, but recovery took much longer. This finding suggested that once the spleen cells had eliminated the autoimmune response, surviving pancreatic cells could grow and establish a new insulin-producing population. Details of this study were published in the November 14, 2003, issue of Science.

"We have found that it is possible to rapidly re-grow an adult organelle without the use of embryonic stem cells,” said senior author Dr. Denise Faustman, an associate professor of medicine at Harvard Medical School. "By accomplishing effective, robust, and durable regeneration of islets, this discovery opens up an entirely new approach to diabetes treatment. We have found that islet regeneration was occurring and that cells were growing from both the recipient's own cells and from the donor cells.”