STEM CELL MICROPARTICLES AND miRNA

Abstract

This invention relates to stem cell microparticles and miRNA isolated from these microparticles, their use and production thereof, in particular neural stem cell microparticles and their use in therapy of cancer, typically a nestin-positive cancer. The cancer may be glioma, melanoma, breast cancer, pancreatic cancer or prostate cancer. The stem cell microparticle is typically an exosome or microvesicle and may be derived from a neural stem cell line. The neural stem cell line may be a conditionally-immortalised stem cell line such as CTX0E03 (deposited at the ECACC with Accession No. 04091601).

What is claimed is: 
     
         1 . A method for treating cancer, comprising administering to a subject in need thereof an exosome isolated from a stem cell, wherein the exosome is loaded with one or more exogenous nucleic acids, lipids, proteins, drugs, prodrugs, therapeutic or diagnostic agents. 
     
     
         2 . The method according to  claim 1 , wherein the stem cell is a neural stem cell. 
     
     
         3 . The method according to  claim 1 , wherein the exosome is loaded with an exogenous nucleic acid that is a coding, non-coding or regulatory nucleic acid. 
     
     
         4 . The method according to  claim 2 , wherein the exosome is loaded with an exogenous nucleic acid that is a coding, non-coding or regulatory nucleic acid. 
     
     
         5 . The method according to  claim 1 , wherein the exosome is loaded with an exogenous therapeutic protein. 
     
     
         6 . The method according to  claim 2 , wherein the exosome is loaded with an exogenous therapeutic protein. 
     
     
         7 . The method according to  claim 1 , wherein the cancer is glioma. 
     
     
         8 . The method according to  claim 7 , wherein the glioma is nestin-positive glioma. 
     
     
         9 . The method according to  claim 8 , wherein the treatment comprises inhibiting migration of the glioma cells. 
     
     
         10 . The method according to  claim 8 , wherein the treatment comprises inducing differentiation of the glioma cells. 
     
     
         11 . The method of  claim 1 , wherein the exosome is isolated from a neural stem cell that:
 (a) is proliferating;   (b) does not express doublecortin or glial fibrillary acidic protein; and/or   (c) has been cultured in a multi-compartment bioreactor for less than 4 weeks and optionally no more than 1 week.   
     
     
         12 . The method of  claim 1 , wherein the exosome is isolated from a neural stem cell line. 
     
     
         13 . The method of  claim 12 , wherein the neural stem cell line is conditionally-immortalised and/or grown in serum free medium. 
     
     
         14 . The method of  claim 12 , wherein the neural stem cell line is a stem cell line selected from the group of: CTX0E03 having ECACC Accession No. 04091601, STR0005 having ECACC Accession No. 04110301, or HPC0A07 having ECACC Accession No. 04092302. 
     
     
         15 . The method of  claim 1 , wherein the exosome has:
 (a) a size of between 30 nm and 1000 nm, or between 30 and 200 nm, or between 30 and 100 nm, as determined by electron microscopy; or   (b) a density in sucrose of 1.1-1.2 g/ml.   
     
     
         16 . A method of preparing a cancer therapy comprising stem cell exosomes, wherein the method of preparing comprises the step of: loading exogenous protein, nucleic acid, lipid, drug, prodrug, therapeutic agent or diagnostic agent into the stem cell exosomes. 
     
     
         17 . The method of  claim 16  wherein, prior to the loading step, the exosomes are isolated from the cells that produced them, and wherein the loading step comprises direct loading into the exosome of the exogenous protein, nucleic acid, lipid, drug, prodrug, therapeutic agent or diagnostic agent. 
     
     
         18 . The method of  claim 16 , wherein the stem cell that produces the exosome is engineered to introduce the exogenous protein, nucleic acid, lipid, drug, prodrug, therapeutic agent or diagnostic agent into the exosome.