Materials Presenting Notch Signaling Molecules To Control Cell Behavior

• US 20130331343A1
• Filed: 11/08/2011
• Published: 12/12/2013
• 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, Mooney, David J., Bouhadir, Kamal H.
• Granted Patent: US 9,603,894 B2
• Time in Patent Office: Days
• US Class Current: 514/21.4
• 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 cell delivery vehicle comprising a biocompatible hydrogel or polymer and a composition that binds to a Notch receptor.

2. The vehicle of claim 1, wherein said composition is covalently linked to said hydrogel or polymer.

3. The vehicle of claim 1, wherein said Notch receptor comprises Notch-1, Notch-2, Notch-3, or Notch-4.

4. The vehicle of claim 1, wherein said composition comprises Delta-like1, Delta-like3, Delta-like4, Jagged1, or Jagged2.

5. A method of modulating behavior of a target cell, comprising transiently contacting said target cell with the vehicle of claim 1.

6. A method of inducing differentiation of a mesenchymal stem cell comprising transiently contacting said mesenchymal stem cell with a cell delivery vehicle comprising a biocompatible hydrogel or polymer and a composition that binds to a Notch receptor, wherein said composition comprises human Jagged-1 or a fragment thereof.

7. The method of claim 6, further comprising contacting said mesenchymal stem cell with an osteogenic induction factor, wherein said mesenchymal stem cell differentiates into a cell of osteogenic lineage.

8. The method of claim 6, further comprising contacting said mesenchymal stem cell with angiotensin or insulin like growth factor-1, wherein said mesenchymal stem cell differentiates into a cell of adipogenic lineage.

9. A method for promoting tissue repair or regeneration comprising introducing into a mammal a cell delivery vehicle, said vehicle comprising a biocompatible hydrogel or polymer to which a composition that binds to a Notch receptor is linked and a stem cell therein.

10. The method of claim 9, wherein said tissue comprises bone, cartilage, or adipose tissue.