Prolonging survival of platelets using CMP-sialic acid,UDP-galactose or both
View Patent ↗The present invention provides modified platelets having a reduced platelet clearance and methods for reducing platelet clearance. Also provided are compositions for the preservation of platelets. The invention also provides methods for making a pharmaceutical composition containing the modified platelets and for administering the pharmaceutical composition to a mammal to mediate hemostasis.
1. A method for increasing the circulation time of a population of platelets comprising contacting an isolated population of platelets with an amount of two or more glycan modifying agents, wherein the agents comprise CMP-sialic acid and UDP-galactose, sufficient to thereby produce a modified platelet population having surface glycan residues modified at their terminus, wherein the population of modified platelets when transplanted into a mammal can circulate in the mammal for at least as long as unmodified platelets.
2. The method of claim 1 , further comprising chilling the population of platelets prior to, concurrently with, or after contacting the platelets with the glycan modifying agent at a temperature in a range between about 0° C. and about 15° C.
3. The method of claim 1 , further comprising storing the population of platelets at room temperature prior to, concurrently with, or after contacting the platelets with the glycan modifying agent at a temperature ranging between about 18° C. and about 25° C.
4. The method of claim 2 or 3 , wherein the population of platelets retains substantially normal hemostatic activity when transplanted into a mammal.
5. The method of claim 2 or 3 , wherein the population of platelets when transplanted into a mammal, has a circulation half-life of about 5% or greater than the circulation half-life of unmodified platelets.
6. The method of claim 1 , wherein the modified platelet population is suitable for transplantation into a human.
7. The method of claim 2 , further comprising chilling the population to a temperature ranging between about 0° C. and about 4° C.
8. The method of claim 2 , further comprising chilling the population to a temperature in a range between about 4° C. and about 15° C.
9. A method for increasing the storage time of platelets, comprising contacting an isolated population of platelets with an amount of two or more glycan modifying agents, wherein the agents comprise CMP-sialic acid and UDP-galactose, sufficient to thereby produce a modified platelet population having surface glycan residues modified at their terminus, and chilling the platelets at a temperature ranging between about 0° C. and about 15° C. to reduce the growth of microorganisms in the platelet population, thereby increasing the storage time of the population of platelets.
10. The method of claim 9 , further comprising chilling the population of platelets prior to, concurrently with, or after contacting the platelets with the glycan modifying agent.
11. The method of claim 10 , wherein the population of platelets retains substantially normal hemostatic activity when transplanted into a mammal.
12. The method of claim 10 , wherein the population of platelets when transplanted into a mammal, has a circulation half-life of about 5% or greater than the circulation half-life of unmodified platelets.
13. The method of claim 9 , wherein the modified platelet population is suitable for transplantation into a human.
14. The method of claim 9 , further comprising chilling the population to a temperature ranging between about 0° C. and about 4° C.
15. The method of claim 9 , further comprising chilling the population to a temperature in a range between about 4° C. and about 15° C.
16. A method for increasing the storage time of platelets, comprising contacting an isolated population of platelets with an amount of CMP-sialic acid and UDP-galactose, sufficient to thereby produce a modified platelet population having surface glycan residues modified at their terminus, and storing the platelets at a temperature ranging between about 18° C. and about 25° C. thereby increasing the storage time of the population of platelets.
17. A method for increasing the storage time of platelets, comprising the steps of:
a) contacting an isolated population of platelets with an amount of one or more glycan modifying agents, wherein the one or more agents comprise CMP-sialic acid, sufficient to thereby produce a modified platelet population having surface glycan residues modified at their terminus, and
b) chilling the platelets at a temperature ranging between about 0° C. and about 15° C. to reduce the growth of microorganisms in the platelet population, thereby increasing the storage time of the population of platelets, wherein the chilled modified platelet population is stored for a period between about 3 days and about 28 days.
18. The method of claim 17 , further comprising chilling the population of platelets prior to, concurrently with, or after contacting the platelets with the glycan modifying agent.
19. The method of claim 17 , wherein the population of platelets retains substantially normal hemostatic activity when transplanted into a mammal.
20. The method of claim 17 , wherein the population of platelets when transplanted into a mammal, has a circulation half-life of about 5% or greater than the circulation half-life of unmodified platelets.
21. The method of claim 17 , wherein the modified platelet population is suitable for transplantation into a human.
22. A method for increasing the circulation time of a population of platelets comprising the steps of:
a) contacting an isolated population of platelets with an amount of one or more glycan modifying agents, wherein the one or more agents comprise CMP-sialic acid, sufficient to thereby produce a modified platelet population having surface glycan residues modified at their terminus, and
b) chilling the platelets at a temperature ranging between about 0° C. and about 15° C., wherein the platelets are chilled for a period between about 3 days and about 28 days;
wherein the population of modified platelets when transplanted into a mammal can circulate in the mammal for at least as long as unmodified platelets.
23. The method of claim 22 , wherein the population of platelets retains substantially normal hemostatic activity when transplanted into a mammal.
24. The method of claim 22 , wherein the population of platelets when transplanted into a mammal, has a circulation half-life of about 5% or greater than the circulation half-life of unmodified platelets.
25. The method of claim 22 , wherein the modified platelet population is suitable for transplantation into a human.