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Generation of insulin-expressing cells from mouse embryonic stem cells.

Milne HM, Burns CJ, Kitsou-Mylona I, Luther MJ, Minger SL, Persaud SJ, Jones PM

Beta Dell Development and Function Group, Division of Reproductive Health Endocrinology and Development, GKT School of Biomedical Sciences, King's College London, London SE1 1UL, UK.

The therapeutic potential of transplantation of insulin-secreting pancreatic beta-cells has stimulated interest in using pluripotent embryonic stem (ES) cells as a starting material from which to generate insulin secreting cells in vitro. Mature beta-cells are endodermal in origin so most reported differentiation protocols rely on the identification of endoderm-specific markers. However, endoderm development is an early event in embryogenesis that produces cells destined for the gut and associated organs in the embryo, and for the development of extra-embryonic structures such as the yolk sac. We have demonstrated that mouse ES cells readily differentiate into extra-embryonic endoderm in vitro, and that these cell populations express the insulin gene and other functional elements associated with beta-cells. We suggest that the insulin-expressing cells generated in this and other studies are not authentic pancreatic beta-cells, but may be of extra-embryonic endodermal origin.

Published 7 February 2005 in Biochem Biophys Res Commun, 328(2): 399-403.
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