Pancreatic islet cell growth factors

Patent Number: 6967100

This patent teaches how to generate islet-like cells from fetal progenitors by culturing in the presence of one of the bone morphogenic proteins together with laminin or a laminin-like extracellular matrix. The patent has 3 independent claims all covering essentially the same process. The first one covers induction of growth and proliferation of "mammalian pancreatic epithelial cells into three-dimensional cystic-ductular structures containing insulin-secreting cells". The second teaches "A method of stimulating or otherwise facilitating formation of colonies of mammalian pancreatic epithelial cells" and the third "A method of stimulating or otherwise facilitating formation of cystic epithelial colonies ". The use of bone morphogenic proteins has since become very common in numerous areas regenerative medicine not limited to islet generation. The author of the patent published that fetal cells obtained from mice at 15.5 day of pregnancy, when cultured in laminin-1 coated plates together with BMP-4, 5 and -6, led to the development of cystic epithelial colonies that contained E-cadherin-positive epithelial cells, which expressed insultin (ie endocrine) but not somatostatin or alpha-amylase (exocrine) (Jiang FX, et al. Bone morphogenetic proteins promote development of fetal pancreas epithelial colonies containing insulin-positive cells. J Cell Sci. 2002 Feb 15;115(Pt 4):753-60). Another laboratory demonstrated that expansion of pancreatic epithelial cells by BMP-4 occurs through, in part, activation of the Inhibitor of DNA binding (Id) protein-2 (Id-2), which in turn binds to and inhibit the function of basic helix-loop-helix (bHLH) transcription factors (Hua H et al. BMP4 regulates pancreatic progenitor cell expansion through Id2 J Biol Chem. 2006 May 12;281(19):13574-80.).

View this patent on the USPTO website.