Placenta-derived adherent cell exosomes and uses thereof

Abstract

Provided herein are compositions of placenta-derived adherent cell exosomes and methods of making and using the same. In one aspect, provided herein are compositions comprising exosomes produced by and/or derived from placental cells, e.g., placenta-derived adherent cells. In certain embodiments, the exosomes provided herein are produced by placenta-derived adherent cells that have been cultured in vitro for, e.g., 1, 2, 3, 4, 5, 6 or more passages.

What is claimed: 
     
         1 . A composition comprising exosomes derived from human placenta-derived adherent cells, wherein said exosomes are CD9 + , CD10 + , CD13 + , CD29 + , CD44 + , CD49b + , CD49c + , CD55 + , CD59 + , CD63 + , CD73 + , CD81 + , CD82 + , CD90 + , CD98 + , CD105 + , CD141 + , CD142 + , CD151 + , CD164 + , CD295 + , or CD200 + . 
     
     
         2 . The composition of  claim 1 , wherein said exosomes are CD9 + , CD10 + , CD13 + , CD29 + , CD44 + , CD49b + , CD49c + , CD55 + , CD59 + , CD63 + , CD73 + , CD81 + , CD82 + , CD90 + , CD98 + , CD105 + , CD141 + , CD142 + , CD151 + , CD164 + , CD295 +  and CD200 + . 
     
     
         3 . The composition of  claim 1  or  2 , wherein said exosomes are CD3−, CD11b−, CD14−, CD19−, CD33−, CD192−, HLA-A−, HLA-B−, HLA-C−, HLA-DR−, CD11c− or CD34−. 
     
     
         4 . The composition of any of  claims 1 - 3 , wherein said exosomes are CD3−, CD11b−, CD14−, CD19−, CD33−, CD192−, HLA-A−, HLA-B−, HLA-C−, HLA-DR−, CD11c− and CD34−. 
     
     
         5 . The composition of any one of  claims 1 - 4 , wherein said exosomes comprise non-coding RNA molecules. 
     
     
         6 . The composition of  claim 5 , wherein said RNA molecules are microRNAs. 
     
     
         7 . The composition of  claim 6 , wherein said microRNAs are miR-218-5p, miR-133b, miR-422a, miR-564, miR-16-5p, let-7a, miR-92, miR-142-3p, miR-451, miR-124-5p, miR-223-3p, miR-630, miR-296-5p, let-7b-3p or let-7d-3p. 
     
     
         8 . The composition of any of  claims 1 - 7 , wherein said exosomes comprise at least one marker molecule at a level at least two-fold higher than exosomes derived from mesenchymal stem cells. 
     
     
         9 . The composition of any of  claims 1 - 8 , wherein said placenta-derived adherent cells have been passaged more than 3 times. 
     
     
         10 . The composition of any of  claims 1 - 9 , wherein said placenta-derived adherent cells have been maintained in culture for greater than 24 hours. 
     
     
         11 . The composition of any of  claims 1 - 10 , wherein at least 90% of said placenta-derived adherent cells are non-maternal in origin. 
     
     
         12 . The composition of any of  claims 1 - 11 , wherein at least 99% of said placenta-derived adherent cells are non-maternal in origin. 
     
     
         13 . The composition of any of  claims 1 - 12  that is in the a form suitable for intravenous administration. 
     
     
         14 . A method of angiogenesis or vascularization in said subject comprising administering the composition of any one of  claims 1 - 13  to the subject. 
     
     
         15 . A method of modulating the immune system of a said subject comprising administering the composition of any one of  claims 1 - 13  to the subject. 
     
     
         16 . A method of repairing diseased or damages tissue in a subject comprising administering the composition of any one of  claims 1 - 13  to the subject. 
     
     
         17 . The method of any of  claims 14 - 16 , wherein said subject is human. 
     
     
         18 . A composition comprising exosomes derived from human placenta-derived adherent cells, wherein said exosomes are CD10 +  and CD55 + . 
     
     
         19 . A method of loading placenta-derived adherent cell exosomes with exogenous agents, comprising incubating a placenta-derived adherent cell exosome and an exogenous agent, such that the exogenous agent is loaded in the exosome. 
     
     
         20 . The method of  claim 19 , wherein the incubation is performed at room temperature. 
     
     
         21 . The method of  claim 19  or  20 , which comprises a step of saponin permeabilization. 
     
     
         22 . The method of  claim 19  or  20 , which does not comprise a step of saponin permeabilization. 
     
     
         23 . The method of  claim 19  or  20 , which comprises one or more freeze/thaw cycles. 
     
     
         24 . The method of  claim 19  or  20 , which comprises a step of sonication. 
     
     
         25 . The method of  claim 19  or  20 , which comprises a step of extrusion. 
     
     
         26 . A method of administering placenta-derived adherent cell exosomes comprising exogenous agents to an individual. 
     
     
         27 . The method of  claim 26 , wherein the exogenous agents comprise a human, humanized, or chimeric antibody, or antigen-binding fragment thereof. 
     
     
         28 . The method of  claim 26 , wherein the exogenous agents comprise one or more gene-modifying components. 
     
     
         29 . The method of  claim 28 , wherein the gene-modifying components comprise a CRISPR-Cas system. 
     
     
         30 . The method of  claim 29 , wherein the CRISPR-Cas system comprises a guide RNA and an endonuclease. 
     
     
         31 . A composition comprising placenta-derived adherent cell exosomes comprising one or more exogenous agents. 
     
     
         32 . The composition of  claim 31 , wherein the exogenous agents comprise a human, humanized, or chimeric antibody, or antigen-binding fragment thereof. 
     
     
         33 . The composition of  claim 31 , wherein the exogenous agents comprise one or more gene-modifying components. 
     
     
         34 . The composition of  claim 33 , wherein the gene-modifying components comprise a CRISPR-Cas system. 
     
     
         35 . The composition of  claim 34 , wherein the CRISPR-Cas system comprises a guide RNA and an endonuclease. 
     
     
         36 . A method of delivering an exogenous agent to a target cell, wherein the exogenous agent is loaded into a placenta-derived adherent cell exosome. 
     
     
         37 . The method of  claim 36 , wherein the target cell is a cell other than the cell type from which the exosome was obtained. 
     
     
         38 . The method of  claim 36  or  37 , wherein the exogenous agents comprise a human, humanized, or chimeric antibody, or antigen-binding fragment thereof. 
     
     
         39 . The method of  claim 36  or  37 , wherein the exogenous agents comprise one or more gene-modifying components. 
     
     
         40 . The method of  claim 38 , wherein the gene-modifying components comprise a CRISPR-Cas system. 
     
     
         41 . The method of  claim 39 , wherein the CRISPR-Cas system comprises a guide RNA and an endonuclease.