Methods and compositions for provision of angiogenic factors

Abstract

Disclosed herein are methods and compositions for the use of marrow adherent stem cells and their descendents; e.g., bone marrow-derived neural regenerating cells; for provision of angiogenic factors to cells. In certain embodiments, provision of angiogenic factors to sites of neural degeneration stimulates growth and/or survival of host neurons.

What is claimed is: 
     
         1 . A method for providing an angiogenic factor to a cell, the method comprising transplanting a bone marrow-derived cell to a subject, wherein the bone marrow-derived cell is obtained by a process comprising the steps of:
 (a) contacting a culture of marrow adherent stromal cells with a polynucleotide comprising sequences encoding a Notch intracellular domain;   (b) selecting cells that comprise the polynucleotide; and   (c) culturing the cells of step (b) to obtain a population of bone marrow-derived cells.   
     
     
         2 . The method of  claim 1 , wherein the angiogenic factor is selected from the group consisting of one or more of vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), bone morphogenetic protein 4 (BMP-4), Dickkopf-1 (Dkk-1), fibroblast growth factor-7 (FGF-7), heparin-binding epidermal growth factor-like growth factor (HB-EGF), interleukin-6 (IL-6), interleukin-8 (IL-8), matrix metalloproteinase-1 (MMP-1), monocyte chemoattractant protein-1 (MCP-1), platelet-derived growth factor AA (PDGF-AA), and transforming growth factor alpha (TGF-α). 
     
     
         3 . The method of  claim 1 , wherein the bone marrow-derived cell is transplanted to a site of neural degeneration in the subject. 
     
     
         4 . The method of  claim 3 , wherein the angiogenic factor facilitates recovery of damaged or dying neural cells in the subject by exerting a regenerative effect. 
     
     
         5 . The method of  claim 4 , wherein the regenerative effect comprises stimulating growth of neurons. 
     
     
         6 . The method of  claim 4 , wherein the regenerative effect comprises promoting survival of neurons. 
     
     
         7 . The method of  claim 4 , wherein the regenerative effect comprises preventing death of neurons. 
     
     
         8 . The method of  claim 4 , wherein the regenerative effect comprises stimulating the growth of endothelial cells 
     
     
         9 . The method of  claim 4 , wherein the regenerative effect comprises stimulating the growth of blood vessels 
     
     
         10 . The method of  claim 3 , wherein the site of neural degeneration is in the central nervous system. 
     
     
         11 . The method of  claim 3 , wherein the site of neural degeneration is in the peripheral nervous system. 
     
     
         12 . The method of  claim 1 , wherein the Notch intracellular domain comprises amino acids 1703-2504 of the Notch-1 protein.