Regenerative medicine for diabetes treatment.

Division of Immunogenetics, Department of Pediatrics, Rangos Research Center, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
Discovery medicine (Impact Factor: 3.63). 04/2005; 5(26):142-7.
Source: PubMed


Extract: Type 1 diabetes (T1D) is an autoimmune disease in which insulin-producing beta-cells contained within the pancreatic islet of Langerhans are destroyed by autoreactive T cells. T1D patients are treated via insulin hormone replacement therapy by subcutaneous injection of recombinant insulin (produced by molecular engineering). Blood glucose levels must be monitored many times a day to determine the appropriate quantity of insulin to be injected in order to control blood glucose levels (glycemia). Under the insulin-based treatment, the large and sustained effort that a patient must make to strive for near optimal control of glycemia over many decades, frequently beginning in childhood, often make this approach impractical. As a result, T1D contributes substantially to the high rate of nephropathy, neuropathy, retinopathy, and generalized microvascular disease experienced by this population. Since insulin replacement therapy alone does not completely protect these individuals from severe complications, more appropriate treatments for curing T1D are needed. Transplantation of the whole pancreas or isolated pancreatic islets, have both been proposed in the aim of more effectively treating patients with complicated T1D. However, tempering the initial enthusiasm over transplantation has been the reported worsened survival rate for recipients of the pancreas alone, when compared with the survival of waiting-list patients receiving conventional insulin therapy, and the follow-up studies on islet recipients in which a gradual loss of islet function has been observed with time.

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    ABSTRACT: 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 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, whereas 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 becomes insufficient for the body's needs. Clinical solutions aimed at avoiding cumbersome daily insulin administrations by the reestablishment 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 administered to prevent rejection. However, new accumulating evidence suggests that, once autoimmunity is abrogated, 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. The safe induction of an autoimmunity-free status might become a new promising therapy for T1D.
    Pharmaceutical Research 03/2006; 23(2):227-42. DOI:10.1007/s11095-005-9095-6 · 3.42 Impact Factor
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    ABSTRACT: Type 1 Diabetes (T1D) is an autoimmune disease resulting from the destruction of pancreatic insulin-producing beta cells that most frequently occurs in genetically predisposed children. Recent observations illustrating the regenerative capability of the endocrine pancreas in addition to advances in stem cell and gene therapy technologies enable the exploration of alternatives to allogeneic islet transplantation. Living-cell-mediated approaches can abrogate autoimmunity and the consequent destruction of beta cells without the need for immunosuppressive drugs. Such approaches can be used as a foundation for new protocols that more easily translate to the clinical setting. The twin goals of controlling autoimmune disease and promoting stable regeneration of insulin-producing beta cells should be considered the cornerstones of the successful development of a cure for this chronic disease.
    Trends in Biotechnology 12/2006; 24(11):516-22. DOI:10.1016/j.tibtech.2006.08.007 · 11.96 Impact Factor
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