Endocrine Abstracts (2006) 11 S10

Stem cells: regeneration in type 1 diabetes

M Trucco1,2

1Children’s Hospital of Pittsburgh, Pittsburgh, PA, United States; 2University of Pittsburgh, Pittsburgh, PA, United States.

Type 1 diabetes (T1D) is an autoimmune disease, the clinical onset of which most frequently presents in children and adolescents who are genetically predisposed. T1D is characterized by a T-cell mediated, specific, insulin-producing beta cell destruction. The well-differentiated and specialized islet beta cells seem to physiologically retain the ability to compensate for the cells lost by reproducing themselves, while undifferentiated cell sources may help in generating new ones, even while the autoimmune process takes place. Diabetes clinical onset, i.e., establishment of a detectable, chronic hyperglycemia, occurs at a critical stage when autoimmunity, having acted for a while, supersedes the regenerative effort and reduces the number of beta cells below the physiologic threshold at which the produced insulin is insufficient for the body’s needs. Clinical solutions aimed at avoiding cumbersome daily insulin administrations by the re-establishment of physiologic insulin production, like whole pancreas or pancreatic islet allotransplantation, are limited by the scarcity of pancreas donors and by the toxic effects of the immunosuppressive drugs (i.e., calcineurin inhibitors) administered to prevent rejection and autoimmunity recurrence. However, new accumulating evidence suggests that once autoimmunity is abrogated using non-diabetogenic means, the endocrine pancreas properties may be sufficient to allow the physiological regenerative process to restore endogenous insulin production, even after the disease has become clinically manifest. Knowledge of these properties of the endocrine pancreas suggests the testing of reliable and clinically-translatable protocols for obliterating autoimmunity, thus allowing the regeneration of the patient’s own endocrine cells. Safe, gene therapy-based approaches can be used to permanently obliterate autoimmunity by restoring central and peripheral tolerance. The safe induction of an autoimmunity-free status might become a new promising therapy for T1D, since by correcting hyperglycemia using conventional insulin administration or an islet allotransplant, ‘nature’ will be left to spontaneously heal the endocrine damage.

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