Research ArticleType 1 Diabetes

Mixed Chimerism and Growth Factors Augment β Cell Regeneration and Reverse Late-Stage Type 1 Diabetes

Science Translational Medicine  09 May 2012:
Vol. 4, Issue 133, pp. 133ra59
DOI: 10.1126/scitranslmed.3003835

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Two Treatments Are Better than One

The mission of the immune system is to defend the body, fighting off infections and cancer. However, sometimes, immune cells mistake healthy normal cells for dangerous foreign invaders. Type 1 diabetes develops when immune cells attack and destroy the insulin-producing β cells in the pancreatic islets. In the absence of insulin, glucose levels increase in the blood and urine, which can be fatal if untreated.

The only curative treatment for type 1 diabetes is islet transplantation, but this therapy is restricted by limited donor availability and lifelong immunosuppression for the recipients. Moreover, islet transplants only last about 3 years before the islets succumb to chronic rejection. Thus, other approaches are being tried. One approach, establishing mixed hematopoietic chimerism, can limit autoimmune destruction of islets but only works before the islets are destroyed. Another, administration of gastrin and epidermal growth factor (EGF), stimulates β cell neogenesis, but does not prevent further autoimmune attack. Now, Wang et al. combine these approaches to cure late-stage type 1 diabetes in a mouse model of type 1 diabetes.

The authors treated nonobese diabetic mice with a combination of a radiation-free, nontoxic conditioning regimen to induce mixed chimerism and gastrin/EGF to induce β cell regeneration. This combination therapy reversed late-stage type 1 diabetes and improved insulin sensitivity. New β cells were formed following this therapy, and these cells survived and accumulated as a result of mixed chimerism-mediated inhibition of the autoimmune reaction. If this success holds true in human patients, this combination therapy may provide an improved curative therapy for type 1 diabetes.