Induction medium and methods for stem cell culture and therapy

Abstract

Novel MSC stem-cell culture and therapy methods and culture medium compositions for the purpose of inducing, activating, or priming discrete uniform cell phenotypes to selectively promote or suppress inflammation and immunity, yielding polarized, primed, activated, or induced cells used in cell-based therapy.

We claim: 
     
         1 . An induction medium comprising:
 (a) a Toll-like receptor 3 (TLR3) ligand,   (b) erythropoietin, and   (c) a hypoxia mimetic.   
     
     
         2 . The induction medium of  claim 1 , wherein the TLR3 ligand is poly(I:C). 
     
     
         3 . The induction medium of  claim 2 , wherein the poly(I:C) is present at a concentration of 0.1 picomolar to 100 mM. 
     
     
         4 . The induction medium of  claim 1 , wherein the TLR3 ligand is poly(A:U). 
     
     
         5 . The induction medium of  claim 4 , wherein the poly(A:U) is present at a concentration of 0.1 picomolar to 100 mM. 
     
     
         6 . The induction medium of  claim 1 , further comprising interleukin 4 (IL-4). 
     
     
         7 . The induction medium of  claim 6 , wherein the IL-4 is present at a concentration of 0.1 picomolar to 100 mM. 
     
     
         8 . The induction medium of  claim 1 , further comprising interleukin 13 (IL-13). 
     
     
         9 . The induction medium of  claim 8 , wherein the IL-13 is present at a concentration of 0.1 picomolar to 100 mM. 
     
     
         10 . The induction medium of  claim 1 , wherein the erythropoietin is present at a concentration of 0.5 mU/ml to 50 mU/ml. 
     
     
         11 . The induction medium of  claim 1 , wherein the hypoxia mimetic is cobalt chloride or desferrioxamine. 
     
     
         12 . The induction medium of  claim 11 , wherein the hypoxia mimetic is present at a concentration of 10 μM to 1 mM. 
     
     
         13 . The induction medium of  claim 1 , which does not comprise serum of human or animal origin. 
     
     
         14 . The induction medium of  claim 1  for use in creating an immunologically polarized mesenchymal stem cell population, wherein the immunologically polarized mesenchymal stem cell population possess anti-inflammatory characteristics marked by expression of anti-inflammatory or immunosuppressive mediators. 
     
     
         15 . A cell culture comprising the induction medium of  claim 1  and a population of stem cells. 
     
     
         16 . The cell culture of  claim 15 , wherein the stem cells are mesenchymal stem cells. 
     
     
         17 . A method for inducing a population of multipotent stem cells to adopt an anti-inflammatory phenotype, the method comprising:
 (a) providing a population of multipotent stem cells; and   (b) culturing the multipotent stem cells in the induction medium of  claim 1 .   
     
     
         18 . The method of  claim 17 , wherein the multipotent stem cells are mesenchymal stem cells.