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Virally-mediated endogenous neogenesis of beta cells yields autoimmune-resistant beta cells

详细技术说明

None

*Abstract

BackgroundType I diabetes mellitus (T1DM) is a chronic illness characterized by the bodyΓÇÖs inability to produce insulin due to the autoimmune destruction of the beta cells in the pancreas.The concept of ╬▓-cell replacement therapy for T1DM seems ill-fated in that the new ╬▓-cells would just quickly succumb to the same autoimmune destruction. In the NOD mouse model of autoimmune diabetes, when diabetic mice receive an islet transplant from syngeneic NOD.SCID mice, the islets undergo a "rapid-recurrent autoimmune rejection" and disappear within days. Thus, a clinically applicable strategy has yet to be developed for T1DM that will lead to an increase in ╬▓-cell mass without the need for immunosuppression.TechnologyDr.Gittes and colleagues have developed a novel AAV system, when introduced into the pancreatic duct, induces neogenesis of beta cells from pre-existing alpha cells. This neogenesis leads to reversal of diabetes in mice in autoimmune NOD mouse, despite the lack of any anti-immune therapy. The failure of the autoimmune cells to attack these neogenic beta cells suggests that they are somehow different from beta cells in their immunogenicity. The immune system of the mice appear unaffected as demonstrated by adoptive transfer experiment. Importantly this approach is potentially immediately applicable to human patients with T1DM .Application - Rescue of autoimmune diabetes without immunosuppression - Potential AAV therapy in T1DM patients, delivered via routine ERCP into the pancreatic ductAdvantages- A novel intraductal viral infusion system - Induction of beta-cell neogenesis from alpha- cells in situ in the islet location in normal and autoimmune mice - Eliminates need for insulin replacement therapy and immune suppressionStage of DevelopmentIn-vivo studies in murine models

*Principal Investigation

Name: George Gittes

Department: Med-Surgery

Name: Ping Guo

Department: Med-Surgery

Name: Xiangwei Xiao

Department: Med-Surgery

国家/地区

美国