Generation of insulin-expressing cells from mouse embryonic stem cells

• Published in: Biochemical and biophysical research communications 2005-03, Vol.328 (2), p.399-403
• Main Authors: Milne, Helen M., Burns, Christopher J., Kitsou-Mylona, Isidora, Luther, Melanie J., Minger, Stephen L., Persaud, Shanta J., Jones, Peter M.
• Format: Article
• Language: English
• Subjects: Animals; Cell Differentiation - physiology; Cells, Cultured; DNA-Binding Proteins - biosynthesis; Embryonic endoderm; Embryonic stem cell; Endoderm - cytology; Endoderm - metabolism; Gene Expression Regulation, Developmental - physiology; Insulin - biosynthesis; Insulin gene; Islets of Langerhans - cytology; Islets of Langerhans - metabolism; Mice; Octamer Transcription Factor-3; Signal recognition; Stem Cells - cytology; Stem Cells - metabolism; Transcription Factors - biosynthesis
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2004.12.183

The therapeutic potential of transplantation of insulin-secreting pancreatic β-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 β-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 β-cells. We suggest that the insulin-expressing cells generated in this and other studies are not authentic pancreatic β-cells, but may be of extra-embryonic endodermal origin.