Regulation of cytotrophoblast cell differentiation and cell migration

Patent Number: 7,244,707

Although this patent describes modulation of stem cell migration in the specification, the claims are restricted to the regulation of placental size. Specifically, the patent claims the use of IGF-2 to augment "placental growth, placental function, placental development and placental differentiation" in a mammal.

The inventors appear to be the first to discover that IGF-2 outcompetes latent TGF-beta for binding to the cation independent mannose 6 phosphate (CIM6P)receptor on trophoblasts. When latent TGF-beta is bound to the CIM6P receptor on trophoblasts, the TGF-beta becomes activated by virtue of urokinase plasminogen cleavage. Active TGF-beta blocks the ability of trophoblasts to migrate. Accordingly the investigators demonstrated that IGF-2 by outcompeting with TGF-beta for binding to the CIMP6 receptor actually increases invasiveness of trophoblasts. Increased trophoblast invasivenss leads to better, more robust, placentas.

Malfunctioning placentas generated by lack of trophoblast invasiveness are a big problem in animal breeding.

The examples section demonstrates that hypoxia increases IGF-2 and also that treatment with IGF-2 increases placental size in mice.

The relation with stem cell migration is not covered in the issued claims but is definately an important area for future investigations.

View this patent on the USPTO website.