Extracellular vesicles and compositions thereof
The current invention relates to a composition comprising extracellular vesicles (EVs) derived from mesenchymal stromal cells (MSCs). The EVs are part of a population of particles in the composition having a particle size of between 0.05 and 0.22 micron. The concentration of these particles is at least 1×10 11 particles per ml of composition. At least 90% of the particles with particle size of between 0.05 and 0.22 micron are EVs. The EVs are defined by having a concentration of intra-vesicular Annexin V of at least 40 ng/ml and a concentration of extra-vesicular Annexin V of less than 1 ng/ml. Uses of the composition also are disclosed.
1 . A pharmaceutical composition comprising Extracellular Vesicles (EVs) derived from Mesenchymal Stromal Cells (MSCs), wherein said particles have a particle size of between 0.05 and 0.22 micron, wherein at least 90% of said particles with a particle size of between 0.05 and 0.22 micron are said EVs, wherein said EVs are associated with Annexin V and human albumin, and wherein said composition comprises said EVs at a ratio of between 5 and 222 μg said EVs associated with Annexin V per g EVs associated with human albumin.
2 . The pharmaceutical composition according to claim 1 , wherein said EVs are further defined by being positive for one or more markers chosen from CD105, CD49, CD44, CD29 or CD142.
3 . The pharmaceutical composition according to claim 1 , wherein said EVs are positive for one or more of EV specific surface markers chosen from SSEA4, HLA1, MSCP or CD29.
4 . The pharmaceutical composition according to claim 1 , wherein said EVs are defined as being HLA class II negative.
5 . The pharmaceutical composition according to claim 1 , wherein said EVs are negative for one or more markers chosen from CD11, CD19, HLA-DR or CD45.
6 . The pharmaceutical composition according to claim 1 , wherein said composition has a human albumin concentration of between 10 and 30 g/L, and wherein at least 90% of said human albumin is associated with said EVs.
7 . The pharmaceutical composition according to claim 1 , wherein said EVs are derived from MSCs derived from perinatal tissues chosen from an umbilical cord, cord blood, placenta, amniotic fluid, amniotic membrane, or from adult tissues chosen from mammary gland, blood, bone marrow, adipose tissue, or dental pulp.
8 . A method of administering a therapeutically effective amount of said pharmaceutical composition of claim 1 to a patient, said patient being an adult, an infant or a neonate, and wherein said pharmaceutical composition is administered at a dose of 10 9 EVs/kg to 10 12 EVs/kg of said patient or for each administration.
9 . The method of claim 8 , wherein said composition is administered for treatment of lung disorders, wherein said lung disorder is an inflammatory lung disease, lung vascular disease, or acute lung injury.
10 . The method of claim 9 , wherein said inflammatory lung disease is pulmonary hypertension, asthma, bronchopulmonary dysplasia (BPD), allergy, or idiopathic pulmonary fibrosis.
11 . The method of claim 9 , wherein said acute lung injury is associated with sepsis or is acute respiratory distress syndrome (ARDS).
12 . The method according to claim 8 , wherein said composition is administered for treatment of Crohn's Disease.