Beta Cell Growth and Differentiation

Description: Significant efforts are currently being directed at the regeneration of functional pancreatic islets from beta-cells, as a possible treatment for Type 1 diabetes. However, the factors that stimulate the growth of beta-cells are not yet well understood. The basis for this invention is the finding that beta-cell replication occurs even in the postdevelopmental state of beta-cell growth. It appears that a coordinated and regulated process of beta-cell replication that is analogous to an epithelial-to-mesenchymal transition plays a role in maintenance of beta-cell mass. This process is believed to be regulated by the homeodomain transcription factor PDX-1. The invention therefore comprises methods of manipulating the signaling pathways leading to PDX-1, to enhance the epithelial-to-mesenchymal transition and increase populations of beta-cells for therapeutic purposes. Clinical & Commercial Utility: The invention features methods of increasing populations of mammalian beta-cells by allowing an initial population of differentiated beta-cells to de-differentiate and then treating these cells with a modulator of a PDX-1 signaling pathway. This method can be carried out ex vivo, to provide an expanded population of cells for islet transplantation, or in vivo, by administration of a pharmaceutical composition to expand the beta-cells within the subject’s body. This method is expected to lead to a reliable, reproducible source of beta-cells for use in cell transplantation protocols for the treatment of Type 1 diabetes.
A U.S. patent application claiming this invention has been filed. The research on which this invention is based has been published, in Kulkarni, et al., J. Clin. Invest. 114:828-836 (2004).

Type of Offer: Licensing

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