Endocrine Abstracts (2007) 13 S22

Replacing beta cells: proof-of-principle and the stem cell option

Neil Hanley

Centre for Human Development, Stem Cells & Regeneration, University of Southampton, www.stemcells.org.uk, Southampton, United Kingdom.

The replacement or regeneration of functional insulin-secreting beta cells is an exciting prospect for the treatment of Type 1 diabetes. Research aimed at this goal must be conducted in a responsible, measured manner in order to maintain public consent and to manage the expectations of patients.

My research group couples investigations of pluripotent stem cell biology with studies of the formation and function of the human endocrine organs during early development. Understanding the latter is anticipated to provide a template for the in vitro differentiation of human stem cell populations to therapeutic end-points.

The transplantation of islets from cadavers provides experimental proof-of-principle for beta cell replacement in Type 1 diabetes. Whereas this clinical therapy remains sub-optimal, it advances the concept that beta cells generated from ex vivo sources offer potential as therapy. My talk will begin by discussing islet transplantation and provide an overview of potential sources of stem cells, from which beta cells might be generated. These data will be placed in the context of our own experiences researching human embryonic stem cells and early human pancreas development. One final consequence of this combined research is that it may be possible to define pathways by which beta cell regeneration might be stimulated endogenously, directly within the pancreas of the patient with Type 1 diabetes. Coupled to advances in immunosuppression, in many respects this combination is highly desirable. My talk will finish by discussing this possibility in relation to our experiences of beta cell formation in response to glucagon-like peptide 1 analogues. These agents are just reaching the market as novel insulin secretagogues licensed for use in Type 2 diabetes.

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