Potential Stem Cell Therapy for Type 1 Diabetes: Potential Stem Cell Therapy for Type 1 Diabetes - Diabetes and Stem Cell Research in Connecticut

Potential Stem Cell Therapy for Type 1 Diabetes: Potential Stem Cell Therapy for Type 1 Diabetes

Xu, Gang., Gibson, Jay., Tian, X. Cindy., Noguchi, Hirofumi., Bonner-Weir, Susan. and Yang, Xiangzhong. "Potential Stem Cell Therapy for Type 1 Diabetes" Paper presented at the annual meeting of the Connecticut's Stem Cell Research International Symposium, TBA, Hartford Connecticut, Mar 27, 2007

Abstract:

Beta cell replacement therapy via islet transplantation is a promising possibility for the optimal treatment of type 1 diabetes. However, such an approach is severely limited by the shortage of donor organs. This problem could be overcome if transplantable islets can be generated from stem cells. We showed previously that adult beta cells could originate from duct or duct-associated cells. Ductal progenitor cells in the pancreas are thus particularly useful target for therapies that target beta cell replacement in diabetic patients, since duct cell types are abundantly available in the pancreas of these patients or in donor organs. We have tested various embryonic transcription factors in adult mouse and human duct cells for their effectiveness in inducing differentiation of ductal cells into insulin producing cells. Transfection with an adenovirus expressing PDX-1, Ngn3, NeuroD, or Pax4 induced expression of the insulin gene. The Pax4 adenovirus strongly induced Ngn3 expression, while Pax 4 is considered the downstream target of Ngn3. These data suggest that over-expression of transcription factors facilitates pancreatic progenitor cell differentiation into insulin-producing cells.
Currently we are examining the potential of embryonic stem (ES) cells differentiation. Specific aims of our research include establishing a protocol for the enrichment of definitive endoderm from murine embryonic stem cells, and investigating the biologic affects of these developmentally associated transcription factors in inducing the differentiation of murine ES cells into pancreatic -like cells. Our goal is to provide useful information with respect to the optimization of differentiation protocols and improvement of -cell function for the treatment of diabetes.