Hydrogel compositions comprising encapsulated cells and methods of use thereof

Abstract

The present invention provides injectable compositions comprising cells encapsulated in hydrogel capsules and methods of preparing these compostions. The present invention also provides methods for using these compositions to promote hematopoiesis and to treat or prevent cardiovascular and immunological disorders in a subject.

1 - 23 . (canceled) 
     
     
         24 . A method of administering at least one protein factor produced by a cell to a subject in need thereof, the method comprising administering to said subject a composition comprising a plurality of hydrogel capsules, wherein at least 90% of said hydrogel capsules in said composition comprise a cell and a hydrogel encapsulating said cell, wherein said hydrogel encapsulating said cell has a thickness of less than 20 microns. 
     
     
         25 . The method of  claim 24 , wherein the cell is a mesencymal stem cell (MSC) or a progenitor thereof. 
     
     
         26 . The method of  claim 24 , wherein the hydrogel in each cell containing hydrogel capsule is characterized by a stiffness of about 0.1 to about 500 kPa. 
     
     
         27 . The method of  claim 24 , wherein each cell containing hydrogel capsule is characterized by a stiffness of about 10 kPa. 
     
     
         28 . The method of  claim 24 , wherein said at least one protein factor is naturally produced by said cell. 
     
     
         29 . The method of  claim 24 , wherein said at least one protein factor is not naturally produced by said cell, and wherein said cell has been genetically engineered to produce said at least one protein factor. 
     
     
         30 . The method of  claim 24 , wherein said cell has been genetically engineered to modify expression of at least one protein factor. 
     
     
         31 . The method of  claim 25 , wherein said at least one protein factor is a hematopoietic factor. 
     
     
         32 . The method of  claim 31 , wherein said hematopoietic factor is selected from the group consisting of stem cell factor (SCF), interleukin-2 (IL-2), interleukin-3 (IL-3), interleukin-6 (IL-6), interleukin-7 (IL-7), granulocyte-macrophage colony stimulating factor (GM-CSF), granulocyte colony stimulating factor (G-CSF), macrophage colony stimulating factor (M-CSF), erythropoietin, thrombopoietin, collagen-I, interleukin-11 (IL-11), angiopoietin-1 and transforming growth factor-beta (TGF-beta). 
     
     
         33 . The method of  claim 24 , wherein the subject is a human. 
     
     
         34 . The method of  claim 25 , wherein the number of hematopoietic stem cells (HSCs) in the subject is increased. 
     
     
         35 . The method of  claim 25 , wherein said at least one protein factor is a cardiovascular regeneration factor. 
     
     
         36 . The method of  claim 35 , wherein said cardiovascular regeneration factor is selected from the group consisting of vascular endothelial growth factor (VEGF), stromal cell derived factor 1 (SDF-1), tumor necrosis factor-inducible gene 6 protein (TSG-6), interleukin-6 (IL-6), interleukin-8 (IL-8), basic fibroblast growth factor (bFGF or FGF-2), insulin-like growth factor 1 (IGF-1), hepatocyte growth factor (HGF), thrombospondin-4, secreted frizzled-related protein 2 (Sfrp2), matrix metalloproteinase 9 (MMP-9), tissue inhibitor of metalloproteinases (TIMP) metallopeptidase inhibitor 2 (TIMP-2), monocyte chemotactic protein 1 (MCP-1), thrombospondin 1 (TSP-1), chemokine (C-X-C motif) ligand 6 (CXCL6) and interferon gamma-induced protein 10 (IP-10). 
     
     
         37 . The method of  claim 25 , wherein said at least one protein factor is a GVHD suppression factor. 
     
     
         38 . The method of  claim 37 , wherein said GVHD suppression factor is selected from the group consisting of transforming growth factor-beta (TGF-beta), hepatocyte growth factor (HGF), prostaglandin E2 (PGE2), galectin and indoleamine 2,3-dioxygenase (IDO). 
     
     
         39 . The method of  claim 24 , wherein the composition is administered by a route selected from the group consisting of intravenous infusion, intrabone infusion, intramuscular injection, subcutaneous implantation, intraperitoneal injection, intracardial injection, intratracheal administration, topical application and oral administration. 
     
     
         40 . The method of  claim 39 , wherein the composition is administered by intravenous infusion. 
     
     
         41 . The method of  claim 34 , wherein the subject has undergone bone marrow transplantation or HSC transplantation. 
     
     
         42 . The method of  claim 34 , wherein the subject suffers from cancer, an immune deficiency disorder, or a blood disease. 
     
     
         43 . The method of  claim 42 , wherein the cancer is a blood cancer or a solid tumor cancer. 
     
     
         44 - 74 . (canceled)