LPS Priming of Stromal Cells to Generate LPS-Specific Exosome Educated Macrophages

Abstract

The disclosure relates to an ex vivo generated population of educated macrophages specific to LPS and methods of making and using such macrophages.

We claim: 
     
         1 . A method for generating an educated macrophage, the method comprising the steps of:
 isolating extracellular vesicles from a mesenchymal stem cell previously exposed to lipopolysaccharide (LPS), and   co-culturing a CD14+ cell with the extracellular vesicles in vitro until the CD14+ cell acquires an anti-inflammatory macrophage phenotype.   
     
     
         2 . The method of  claim 1 , wherein the CD14+ cell and the extracellular vesicles are co-cultured for at least 2 days. 
     
     
         3 . The method of  claim 1 , wherein the mesenchymal stem cell was exposed to LPS for at least 2 hours. 
     
     
         4 . The method of  claim 1 , wherein the mesenchymal stem cell is exposed to about 50 ng/ml to about 200 ng/ml LPS. 
     
     
         5 . A population of anti-inflammatory macrophages produced by the method of  claim 4 , wherein the anti-inflammatory macrophage phenotype is characterized as CD206 high, PD-L1 high, PD-L2 high, CD16 high and CD73 high compared to control macrophages. 
     
     
         6 . The method of  claim 1 , wherein the CD14+ cell is a macrophage. 
     
     
         7 . The method of  claim 1 , wherein the CD14+ cell is a monocyte and wherein the CD14+ monocyte and the extracellular vesicle are co-cultured for at least 5 days.