Materials presenting notch signaling molecules to control cell behavior

• US 9,603,894 B2
• Filed: 11/08/2011
• Issued: 03/28/2017
• Est. Priority Date: 11/08/2010
• Status: Active Grant

• Current Assignee: President and Fellows of Harvard College (Harvard Corporation)
• Original Assignee: President and Fellows of Harvard College (Harvard Corporation)
• Inventors: Cao, Lan, Bouhadir, Kamal H., Mooney, David J.
• Primary Examiner(s): Alstrum Acevedo, James H
• Assistant Examiner(s): Coffa, Sergio
• Application Number:
  US13/883,005
• Publication Number:
  US 20130331343A1
• Time in Patent Office: 1,967 Days
• US Class Current: 1/1
• CPC Class Codes: A61K 38/10 Peptides having 12 to 20 amino acids A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61K 38/1709 from mammals
• CPC Class Codes: A61K 47/61 the organic macromolecular compound being a polysaccharide or a derivative thereof
• CPC Class Codes: A61K 47/64 Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent peptidic linkers A61K47/65

Abstract

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.

Claims

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.