Tesis doctoral de Xavier Anguela Martínez
Development of type 1 diabetes has been attributed to t-cell-mediated autoimmunity which is regulated by antigen-presenting cells. It is currently widely accepted that the liver is a unique immunological organ with unmatched immunomodulatory properties. It is highly enriched in elements particular to the immune system, including cell systems with innate immune capacities such as kupffer cells and sinusoidal endothelial cells, as well as cells participating in adaptive immune responses. Indeed, the liver is regarded as exerting biased immune responses to promote tolerance rather than immunity. we have previously reported that expression of igf-i in íY cells of transgenic mice counteracts cytotoxicity and insulitis after treatment with multiple low doses of streptozotocin (stz). Our results indicated that local expression of igf-i in íY cells regenerates pancreatic islets and counteracts type 1 diabetes (george et al., 2002). In addition, we have shown that pancreatic expression of igf-i prevented islet infiltration and íY cell death in transgenic mice with increased susceptibility to autoimmune diabetes. These results indicated that pancreatic expression of igf-i may protect íY cell mass in this disease (casellas et al., 2006). Moreover, daily subcutaneous administration of human recombinant igf-i to prediabetic nod mice reduced the severity of insulitis and the incidence of t1d (bergerot et al., 1995; chen et al., 2004; kaino et al., 1996). All these studies reveal igf-i as a key factor able to induce protection from type 1 diabetes. in this study we aimed to combine the immunomodulatory properties of the liver with the protective effects of igf-i to develop a non-viral, liver-directed gene therapy approach for type 1 diabetes.
Datos académicos de la tesis doctoral «Overexpression of igf-i in liver prevents the development of type 1 diabetes: a new non-viral gene therapy approach«
- Título de la tesis: Overexpression of igf-i in liver prevents the development of type 1 diabetes: a new non-viral gene therapy approach
- Autor: Xavier Anguela Martínez
- Universidad: Autónoma de barcelona
- Fecha de lectura de la tesis: 30/07/2009
Dirección y tribunal
- Director de la tesis
- Fatima Bosch Tubert
- Tribunal
- Presidente del tribunal: ramon Gomis de barbar?
- federico Mingozzi (vocal)
- (vocal)
- (vocal)