Issue 156 Item 4 Stem Cell Transplant Prevents Autoimmune Diabetes

Syngeneic transplant of hematopoietic stem cells (HSCs) encoding proinsulin antigen prevents autoimmune diabetes. That, according to a report in the May issue of The Journal of Clinical Investigation.

Proinsulin is a key autoantigen that drives pancreatic beta cell destruction in type 1 diabetes, the authors explain, suggesting that induction of tolerance to proinsulin might prevent autoimmune diabetes.

Dr. Leonard Harrison and associates from The Walter and Eliza Hall Institute of Medical Research in Parkville, Victoria, Australia tested whether HSCs from NOD mice in which proinsulin was transgenically targeted to antigen-presenting cells could prevent autoimmune diabetes when transplanted into wild-type NOD mice.

Diabetes was almost completely prevented in recipients of bone marrow from NOD mice bred to encode proinsulin (1 of 16 mice developed diabetes), the authors report, whereas 15 of 23 untreated controls and in 7 of 12 recipients of normal NOD bone marrow developed diabetes.

T cell depletion of transplanted bone marrow did not reduce the protective effect of cells encoding proinsulin. Similarly, diabetes was completely prevented in recipients of proinsulin-encoding HSCs (0 of 10 mice developed diabetes), the results indicate. Transfer of hematopoietic progenitor cells also afforded substantial protection (2 of 14 mice developed diabetes, compared with 8 of 16 controls).

“Complete protection after transfer of highly purified HSCs shows that diabetes prevention depends on the engraftment of multipotent hematopoietic cells and not on the inadvertent transfer of immunoregulatory cells in whole of T cell-depleted bone marrow,” the researchers explain.

The protective effect of HSC or bone marrow transplantation was evident even at low levels of bone marrow engraftment, the investigators observe.

“These results are a proof of principle that autoantigen-expressing HSCs can be used as a therapeutic tool to prevent autoimmune disease,” the authors conclude. “We envisage that HSCs could be harvested from peripheral blood of at-risk individuals, genetically modified to encode autoantigen, and reinfused to prevent autoimmune disease.” J Clin Invest 2003;111:1357-1363.

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