Neural cell extracellular vesicles
Disclosed herein are neural extracellular vesicles (EVs) and methods of using these EVs in the treatment of spinal cord injury, stroke, and traumatic brain injury and neurodegenerative diseases.
1. A method of treating a human subject who has suffered a stroke, comprising administering to the subject an effective amount of a pharmaceutical composition comprising isolated extracellular vesicles (EVs) derived from non-transformed human neural progenitor cells, wherein the EVs are administered intravenously or intranasally.
2. The method of claim 1 , wherein the neural progenitor cells are derived from human pluripotent stem cells.
3. The method of claim 1 , wherein the neural progenitor cells are derived from human induced pluripotent stem cells.
4. The method of claim 1 , wherein the neural progenitor cells are derived from human embryonic stem cells.
5. The method of claim 1 , wherein the subject has suffered an ischemic stroke.
6. The method of claim 1 , wherein the subject has suffered a hemorrhagic stroke.
7. The method of claim 1 , wherein the composition is administered intravenously.
8. The method of claim 1 , wherein the composition is administered intranasally.
9. The method of claim 1 , wherein the composition is initially administered within 24 hours following a stroke.
10. The method of claim 1 , wherein the composition is administered to the subject 1-4 weeks following a stroke.
11. The method of claim 1 , wherein the composition comprises about 1 mg to about 500 mg of EVs.
12. The method of claim 1 , wherein the EVs comprise exosomes.
13. The method of claim 1 , wherein the EVs are about 20 nm to about 150 nm in size.
14. The method of claim 1 , wherein the neural progenitor cells express one or more markers selected from the group consisting of nestin, SOX1, and SOX2, and do not express OCT4.
15. The method of claim 1 , wherein the pharmaceutical composition reduces swelling in the brain of the subject and/or reduces inflammation in the subject.
16. The method of claim 1 , wherein the pharmaceutical composition improves sensorimotor function in the subject and/or improves behavioral function in the subject.
17. The method of claim 1 , wherein the pharmaceutical composition reduces lesion volume in the subject.
18. The method of claim 1 , wherein the EVs further comprise an agent selected from the group consisting of aa small molecule, an antisense oligonucleotide, as siRNA, an exogenous peptide, an exogenous protein, and an antibody.
19. The method of claim 1 , further comprising administering to the subject an additional bioactive agent useful in the treatment of stroke.
20. The method of claim 19 , wherein the additional bioactive agent is selected from the group consisting of a salicylate, a thrombolytic agent, and a platelet aggregation inhibitor.
21. The method of claim 20 , wherein the additional bioactive agent is selected from the group consisting of aspirin, alteplase, and clopidogrel.
22. A method of improving the likelihood of survival of a human subject following a stroke, comprising administering to the subject an effective amount of a pharmaceutical composition comprising isolated extracellular vesicles (EVs) derived from non-transformed human neural progenitor cells, wherein the EVs are administered intravenously or intranasally.
23. The method of claim 22 , wherein the human neural progenitor cells express one or more markers selected from the group consisting of nestin, SOX1, and SOX2, and do not express OCT4.
24. The method of claim 22 , wherein the composition is initially administered within 24 hours following a stroke.
25. The method of claim 22 , wherein the subject has suffered an ischemic stroke.
26. A method of improving sensorimotor function in a human subject following a stroke, comprising administering to the subject an effective amount of a pharmaceutical composition comprising isolated extracellular vesicles (EVs) derived from non-transformed human neural progenitor cells, wherein the EVs are administered intravenously or intranasally.
27. The method of claim 26 , wherein the human neural progenitor cells express one or more markers selected from the group consisting of nestin, SOX1, and SOX2, and do not express OCT4.
28. The method of claim 26 , wherein the composition is initially administered within 24 hours following a stroke.
29. The method of claim 26 , wherein the improvement in sensorimotor function comprises an improvement in the ability to stand unassisted, an improvement in gait velocity, and/or an improvement in gait rhythmicity.
30. The method of claim 26 , wherein the subject has suffered an ischemic stroke.