Enhancement of placental stem cell potency using modulatory rna molecules

Abstract

Provided herein are methods of producing enhanced placental stem cells by modulatory RNA molecules. Also provided herein are methods of using enhanced placental stem cells, for example, to treat individuals having a disease, disorder or condition caused by, or relating to, an unwanted or harmful immune response. Further provided herein are compositions comprising said enhanced placental stem cells.

1 .- 23 . (canceled) 
     
     
         24 . A composition comprising enhanced placental stem cells, wherein said enhanced placental stem cells comprise or have been contacted with an amount of modulatory RNA molecules effective to decrease expression of one or more human nuclear receptors in said enhanced placental stem cells, wherein said enhanced placental stem cells cause greater suppression of soluble IL-23 protein produced by peripheral blood mononuclear cells (PBMCs) than placental stem cells not contacted with said modulatory RNA molecules. 
     
     
         25 . The composition of  claim 24 , wherein said modulatory RNA molecules comprise small interfering RNAs (siRNAs), microRNA inhibitors (miR inhibitors), or micro RNA mimics (miR mimics). 
     
     
         26 . The composition of  claim 24 , wherein said one or more human nuclear receptors is selected from the group consisting of: vitamin D receptor (VDR); nuclear receptor subfamily 4, group A, member 3 (NR4A3); nuclear receptor subfamily 0, group B, member 2 (NROB2); nuclear receptor subfamily 1, group I, member 2 (NR1I2); nuclear receptor subfamily 1, group H, member 3 (NR1H3); and deoxynucleotidyltransferase, terminal, interacting protein 1 (DNTTIP1). 
     
     
         27 . The composition of  claim 25 , wherein said one or more human nuclear receptors is selected from the group consisting of: vitamin D receptor (VDR); nuclear receptor subfamily 4, group A, member 3 (NR4A3); nuclear receptor subfamily 0, group B, member 2 (NROB2); nuclear receptor subfamily 1, group I, member 2 (NR1I2); nuclear receptor subfamily 1, group H, member 3 (NR1H3); and deoxynucleotidyltransferase, terminal, interacting protein 1 (DNTTIP1). 
     
     
         28 . The composition of  claim 25 , wherein said modulatory RNA molecules comprise siRNAs. 
     
     
         29 . The composition of  claim 25 , wherein said modulatory RNA molecules comprise miR inhibitors. 
     
     
         30 . The composition of  claim 25 , wherein said modulatory RNA molecules comprise miR mimics. 
     
     
         31 . The composition of  claim 24 , wherein said modulatory RNA molecules are selected from a library. 
     
     
         32 . The composition of  claim 31 , wherein said library is a human nuclear receptor library, human phosphatase siRNA library, or an anti-miR library. 
     
     
         33 . The composition of  claim 24 , wherein said placental stem cells are CD10 + , CD34 − , CD105 + , CD200 +  placental stem cells. 
     
     
         34 . The composition of  claim 24 , wherein said placental stem cells express CD200 and do not express HLA-G, or express CD73, CD105, and CD200, or express CD200 and OCT-4, or express CD73 and CD105 and do not express HLA-G. 
     
     
         35 . The composition of  claim 33 , wherein said placental stem cells are additionally CD90 +  and CD45 − . 
     
     
         36 . The composition of  claim 33 , wherein said placental stem cells are additionally CD80 −  and CD86 − .