Is Facilitating Pancreatic Beta Cell Regeneration a Valid Option for Clinical Therapy?
Abstract:Type 1 diabetes (T1D) is an autoimmune disease in which the clinical onset most frequently presents in adolescents who are genetically predisposed. There is accumulating evidence that the endocrine pancreas has regenerative properties, that hematopoietic chimerism can abrogate destruction of beta cells in autoimmune diabetes, and that, in this manner, physiologically sufficient endogenous insulin production can be restored in clinically diabetic NOD mice. Recapitulating what also has been seen sporadically in humans, we set out to test reliable and clinically translatable alternatives able to achieve these same goals. Recently, Tian and colleagues demonstrated that T1D can be prevented in genetically susceptible mice by substituting a “diabetes-susceptible” class II MHC beta chain with a “diabetes-resistant” allelic transgene on their hematopoietic stem cells through gene supplantation. The expression of the newly formed diabetes-resistant molecule in the reinfused hematopoietic cells was sufficient to prevent T1D onset even in the presence of the native, diabetogenic molecule. If this approach to obtain autoimmunity abrogation could facilitate a possible recovery of autologous insulin production in diabetic patients, safe induction of an autoimmunity-free status might become a new promising therapy for T1D.
Document Type: Research Article
Affiliations: Division of Immunogenetics, Department of Pediatrics,Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA, USA
Publication date: March 1, 2006
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