EVALUATION OF EFFICACY OF AUTOLOGOUS BONE MARROW STEM CELL TRANSPLANTATION IN TYPE 1 DIABETES MELLITUS

Abstract

T ype 1 diabetes is an autoimmune disease and results from T cell-mediated destruction of insulin-producing pancreatic beta cells. Patients at onset of type 1 diabetes usually have limited beta cell mass and depend on exogenous insulin treatment. The development of new therapies to control T cell autoimmunity and to preserve the remaining beta cell function will be of great significance in managing patients with type 1 diabetes. Autologous hematopoietic stem cell transplantation (AHSCT) has been tested for the treatment of patients with new onset of type 1 diabetes. This therapeutic strategy can result in exogenous insulin independence by destroying pathogenic memory T cells and preserving the remaining beta cell function. Type I autoimmune diabetes develops when one or another immunoregulatory mechanism fails, allowing autoreactive T-cells directed against beta cells to become activated and to expand clonally, starting a cascade of immune/inflammatory processes in the islets (insulitis), causing beta cell destruction. The cytokine profile of T-helper cells is crucial to the development of an effective immune response. Th-1 cells secrete IL-2, IFN-γ and tumor necrosis factor beta (TNF-β) which may cause diabetes in different ways. These mediators may stimulate immune inflammatory responses such as the activation of cytotoxic T-cells. This, in turn, may lead to destruction of pancreatic β-cells and activation of macrophages leading to the secretion of proinflammatory cytokines such as IL-1, TNF-α, IFN-γ and free oxygen or nitrogen radicals which are cytotoxic to beta cells.