Compositions and methods for treating pain with extracellular vesicles
Described herein are cell-free therapeutic compositions derived from blood or plasma and uses thereof for the treatment of selected diseases and disorders.
1. A method of treating a disease or disorder in a subject in need thereof, the method comprising:
administering to the subject having the disease or disorder a therapeutically effective amount of a composition comprising:
blood-derived nanoparticles, the blood-derived nanoparticles having a diameter less than 200 nm, the blood-derived nanoparticles derived from substantially platelet-free and cell-free blood, and
a concentration of blood-derived nanoparticles in the composition being at least 1×10 8 nanoparticles/ml.
2. The method of claim 1 , wherein the composition is made by a process comprising:
(a) obtaining a volume of blood;
(b) centrifuging the volume of blood at 2,000×g for at least 10 minutes (min) to obtain a first supernatant;
(c) centrifuging the first supernatant at 100,000×g for at least 90 min to obtain a pellet comprising the nanoparticles;
(d) isolating and resuspending the pellet in a volume of resuspension fluid to obtain a resuspended volume; and
(e) filtering at least a portion of the resuspended volume using a 0.22 uM filter.
3. The method of claim 1 , wherein the composition is made by a process comprising:
(a) obtaining a volume of blood;
(b) centrifuging the volume of blood at 2,000×g for at least 10 minutes (min) to obtain a first supernatant;
(c) centrifuging the first supernatant at 2,000×g for at least 5 min to obtain a second supernatant;
(d) centrifuging the second supernatant at 100,000×g for at least 90 min to obtain a pellet comprising the nanoparticles;
(e) isolating and resuspending the pellet in a volume of resuspension fluid to obtain a resuspended volume; and
(f) filtering at least a portion of the resuspended volume using a 0.22 uM filter.
4. The method of claim 1 , wherein the disease or disorder is joint pain.
5. The method of claim 4 , wherein the joint pain is derived from arthritis.
6. The method of claim 5 , wherein the arthritis is osteoarthritis or rheumatoid arthritis.
7. The method of claim 4 , wherein the joint is selected from the group consisting of hand, hip, shoulder, and knee.
8. The method of claim 1 , wherein the nanoparticles are extracellular vesicles (EVs).
9. The method of claim 8 , wherein the extracellular vesicles are autologous to the subject.
10. The method of claim 8 , wherein the extracellular vesicles are heterologous to the subject.
11. The method of claim 8 , wherein the extracellular vesicles comprise exosomes.
12. The method of claim 8 , wherein the extracellular vesicles comprise any of the surface-bound proteins CD41a, CD9, CD63, or CD81.
13. The method of claim 12 , wherein the concentration of EVs comprising CD41a is at least 10 7 EVs per mL.
14. The method of claim 12 , wherein the concentration of EVs comprising CD41a ranges from 10 9 to 10 13 EVs per mL.
15. The method of claim 1 , wherein a protein concentration is at least 0.02 mg/mL.
16. The method of claim 1 , wherein a protein concentration ranges from 0.02 to 10 mg/mL.
17. The method of claim 16 , wherein the protein concentration is about 0.045 mg/mL, 2.25 mg/mL, or 4.5 mg/mL.
18. The method of claim 1 , wherein the diameter of the nanoparticles ranges from 20 nm to 200 nm.
19. The method of claim 1 , wherein the diameter of the nanoparticles is, on average, 60 nm.
20. The method of claim 1 , wherein the concentration of the nanoparticles is at least 10 9 particles/mL.
21. The method of claim 20 , wherein the concentration of the nanoparticles is at least 1.0×10 11 particles/mL.
22. The method of claim 1 , wherein the concentration of nanoparticles ranges from 1.0×10 8 particles/mL to 1.0×10 13 particles/mL.
23. The method of claim 1 , wherein the concentration of nanoparticles is about 3.0×10 9 , 1.5×10 11 , or 3.0×10 11 particles per mL.
24. The method of claim 1 , wherein the wherein the composition is administered by intravenous or intraarticular injection.
25. The method of claim 1 , wherein the subject is administered at least one dose of the composition.
26. The method of claim 25 , wherein the subject is administered two doses of the composition.
27. The method of claim 1 , wherein the nanoparticles are derived from the blood of the subject.
28. The method of claim 24 , wherein the volume of the composition administered by intravenous injection is at least 100 mL.
29. The method of claim 24 , wherein the volume of the composition administered by intraarticular injection is about 1 mL or 2 mL.
30. The method of claim 24 , wherein the volume of the composition administered by intraarticular injection is at least 1 mL.