A generic strategy for pharmacological caging of growth factors for tissue engineering

28.05.2013

Karlsson M, Lienemann PS, Sprossmann N, Heilmann K, Brummer T, Lutolf MP, Ehrbar M, Weber W.

Chem Commun (Camb). 2013;49(53):5927-9

Chem Commun (Camb).              online article

The possibility to trap small signaling molecules in cages and to subsequently uncage them in a controlled manner at the site of interest allows for the spatiotemporal manipulation of signaling processes. Caging has successfully been applied to a vast array of small signaling molecules, leading to a revolutionized understanding of the biological processes controlled by these molecules. As many cellular processes rely on proteins rather than on small signaling molecules, the ability to cage proteins in a similar manner is highly desirable. Techniques potentially applicable to the caging of proteins have been reported; however, these are complicated and must be tailored for each specific protein of interest. A method enabling the caging of arbitrary proteins is thus much needed. Here we demonstrate a general procedure utilizing a cage to trap one or several proteins of choice equipped with an Fc-tag, applicable both in vivo and in vitro. Moreover, to address the high demand to manipulate growth factor-controlled signaling pathways, we provide a versatile platform consisting of the cage along with an optimized generic protocol for growth factor production. As an example illustrating the potential of this platform, caged growth factors were used for time-resolved stimulation of mesenchymal progenitor cell migration. The platform is believed to be valuable for many therapeutic applications, for example in tissue engineering and the development of future cancer therapies.