Materials presenting notch signaling molecules to control cell behavior
The invention provides a solution to the problem of delivering molecules in a physiologically relevant manner to direct cell fate. For example, a Notch ligand molecule is presented in a microenvironment that mimics the environment encountered in vivo. Accordingly, the invention features a cell delivery vehicle comprising a biocompatible hydrogel or polymer and a composition that binds to a Notch receptor and methods of directing cell fate, e.g., stem cell differentiation, using such compositions.
1. A method of inducing differentiation of a population of mesenchymal stem cells comprising transiently contacting the population of mesenchymal stem cells with:
a) a biocompatible alginate hydrogel covalently linked to human Jagged-1, said Jagged-1 comprising the amino acid sequence of SEQ ID NO:1, or a fragment thereof, said fragment comprising the amino acid sequence of SEQ ID NO:2 or SEQ ID NO:3, and
b) a bone morphogenetic protein,
thereby inducing differentiation of the population of mesenchymal stem cells into a population of cells of osteogenic lineage, wherein the level of alkaline phosphatase activity of the population of cells after said contacting is increased by at least 4-fold as compared to the level of alkaline phosphatase activity of a population of mesenchymal stem cells that has been contacted with the bone morphogenetic protein but not the alginate hydrogel.
2. The method of claim 1 , wherein said bone morphogenetic protein is bone morphogenetic protein-4.
3. The method of claim 1 , wherein said population of cells of osteogenic lineage comprises bone cells or cartilage cells.
4. The method of claim 2 , wherein said bone morphogenetic protein-4 comprises amino acids 36-275 or 308-408 of SEQ ID NO:4.
5. The method of claim 1 , wherein said alginate hydrogel comprises alginate covalently linked to a peptide molecule comprising an arginine-glycine-aspartic acid (RGD) sequence.