Mesenchymal stem cell particles

Abstract

We describe a particle secreted by a mesenchymal stem cell and comprising at least one biological property of a mesenchymal stem cell. The biological property may comprise a biological activity of a mesenchymal stem cell conditioned medium (MSC-CM) such as cardioprotection or reduction of infarct size. The particle may comprise a vesicle or an exosome.

1 . A pharmaceutical composition comprising:
 a preparation consisting essentially of a fractionation product of serum-free conditioned medium from a human mesenchymal stem cell (MSC) culture, the fractionation product consisting of an exosome-containing retentate, wherein the exosomes in the exosome containing retentate are from 50 to 100 nm in size, wherein the fractionation product is free of calf-serum proteins and has cardioprotective activity; and   a pharmaceutically acceptable excipient, diluent or carrier.   
     
     
         2 . The composition of  claim 1 , in which the exosomes comprise at least 70% of the proteins listed in Table D1 of E2 or are gene products of the genes listed in Table D2, or in which the exosomes comprise one or more miRNAs listed in Table E3. 
     
     
         3 . The composition of  claim 1 , wherein the concentration of 50 nm to 100 nm exosomes in the retentate is about 125 times their concentration in the serum-free conditioned medium. 
     
     
         4 . The composition of  claim 1 , in which the exosomes have a cholesterol-phospholipid ratio greater than 0.4 (mol/mol). 
     
     
         5 . A method of treating a cardiac injury, the method comprising administering to a subject in need thereof a pharmaceutical composition comprising:
 a preparation consisting essentially of a fractionation product of serum-free conditioned medium from a human mesenchymal stem cell (MSC) culture, the fractionation product consisting of an exosome-containing retentate, wherein the exosomes in the exosome containing retentate are from 50 to 100 nm in size, wherein the fractionation product is free of calf-serum proteins and has cardioprotective activity; and   a pharmaceutically acceptable excipient, diluent or carrier.   
     
     
         6 . The composition of  claim 5 , in which the exosomes comprise at least 70% of the proteins listed in Table D1 of E2 or are gene products of the genes listed in Table D2, or in which the exosomes comprise one or more miRNAs listed in Table E3. 
     
     
         7 . The composition of  claim 5 , wherein the concentration of 50 nm to 100 nm exosomes in the retentate is about 125 times their concentration in the serum-free conditioned medium. 
     
     
         8 . The composition of  claim 5 , in which the exosomes have a cholesterol-phospholipid ratio greater than 0.4 (mol/mol). 
     
     
         9 . The method of  claim 5 , wherein the cardiac injury comprises a myocardial infarct or cardiac inflammation. 
     
     
         10 . The method of  claim 5 , wherein the pharmaceutical composition is administered by direct intracoronary injection. 
     
     
         11 . The method of  claim 5 , wherein the pharmaceutical composition is administered via percutaneous catheter under fluoroscopic guidance. 
     
     
         12 . A percutaneous catheter comprising a pharmaceutical preparation consisting essentially of a pharmaceutically acceptable excipient, diluent or carrier and a fractionation product of serum-free conditioned medium from a human mesenchymal stem cell (MSC) culture, the fractionation product consisting of an exosome-containing retentate, wherein the exosomes in the exosome containing retentate are from 50 to 100 nm in size, wherein the fractionation product is free of calf-serum proteins and has cardioprotective activity. 
     
     
         13 . The catheter of  claim 12 , in which the exosomes comprise at least 70% of the proteins listed in Table D1 of E2 or are gene products of the genes listed in Table D2, or in which the exosomes comprise one or more miRNAs listed in Table E3. 
     
     
         14 . The composition of  claim 12 , wherein the concentration of 50 nm to 100 nm exosomes in the retentate is about 125 times their concentration in the serum-free conditioned medium. 
     
     
         15 . The composition of  claim 12 , in which the exosomes have a cholesterol-phospholipid ratio greater than 0.4 (mol/mol).