Retinal pigment epithelium cell compositions

Abstract

Presented herein are ready to administer (RTA) retinal pigment epithelium (RPE) cell therapy compositions for the treatment of retinal degenerative diseases and injuries. A method of formulating human RPE cells for administration to a subject directly after thawing and of formulating RPE cell therapy compositions for cryopreservation and administration of the cryopreserved composition to a subject subsequent to thawing are also presented. In another aspect, the RTA composition may be formulated as a thaw and inject (TAI) composition, whereby the composition is administered by injection subsequent to thawing.

1 - 79 . (canceled) 
     
     
         80 . A composition for treatment of a retinal condition comprising:
 (a) a purine nucleoside, a branched glucan, a zwitterionic organic chemical buffering agent, and dimethyl sulfoxide (DMSO); and   (b) retinal pigment epithelial (RPE) cells, wherein the composition is formulated to be stored at cryothermic temperatures and wherein the composition is ready to administer to a subject directly after thawing.   
     
     
         81 . A method of treating a retinal condition in a subject in need thereof, the method comprising administering to the subject a composition comprising:
 (i) a purine nucleoside, a branched glucan, a zwitterionic organic chemical buffering agent, and dimethyl sulfoxide (DMSO); and   (ii) retinal pigment epithelial (RPE) cells, wherein the composition can be stored at cryothermic temperatures and wherein the composition is ready to administer to a subject directly after thawing.   
     
     
         82 . A method of formulating an RPE cell composition, comprising:
 a) suspending RPE cells to form a cell suspension in a cell preservation media comprising a purine nucleoside, a branched glucan, a zwitterionic organic chemical buffering agent, and dimethyl sulfoxide (DMSO); and   b) storing the cell suspension at a cryothermic temperature; wherein at least about 60% of the cells are viable after thawing the cell suspension.   
     
     
         83 . The method of  claim 82 , wherein the RPE cell composition is ready to administer to a subject directly after thawing. 
     
     
         84 . The method of  claim 82 , wherein the purine nucleoside is adenosine, the branched glucan is dextran-40, the zwitterionic organic chemical buffering agent is HEPES (N-(2-Hydroxyethyl) piperazine-N′-(2-ethanesulfonic acid)), and the cell preservation media further comprises L-glutathione. 
     
     
         85 . The method of  claim 82 , wherein the RPE cell composition is for the treatment of a retinal condition. 
     
     
         86 . The method of  claim 85 , wherein the retinal condition comprises non-exudative age related macular degeneration (AMD). 
     
     
         87 . The method of  claim 82 , further comprising loading the RPE cell composition into a delivery device after thawing. 
     
     
         88 . The method of  claim 87 , wherein the delivery device comprises a needle. 
     
     
         89 . The method of  claim 82 , the RPE cell composition comprising between about 0.5% and about 7% DMSO. 
     
     
         90 . The method of  claim 82 , the RPE cell composition comprising between about 1.5% and about 6.5% DMSO. 
     
     
         91 . The method of  claim 82 , the RPE cell composition comprising between about 1.5% and about 3% DMSO. 
     
     
         92 . The method of  claim 82 , the RPE cell composition comprising between about 4% and about 6% DMSO. 
     
     
         93 . The method of  claim 82 , wherein the RPE cell composition is not washed or reconstituted prior to administering to the subject. 
     
     
         94 . The method of  claim 82 , wherein dead cells are not removed from the RPE cell composition prior to administration to the subject. 
     
     
         95 . The method of  claim 82 , wherein the RPE cell composition is stored at the cryothermic temperatures from about 1 month to about 48 months. 
     
     
         96 . The method of  claim 82 , wherein the cryothermic temperature is from about −4° C. to about −200° C., or from about −20° C. to −200° C., or from about −70° C. to −196° C., or from about −4° C. to −196° C. 
     
     
         97 . The method of  claim 82 , wherein the RPE cells demonstrate one or more of tight junctions, generation of blood-retinal barriers, or polarized PEDF and VEGF secretion after administration to the subject. 
     
     
         98 . The method of  claim 82 , wherein the RPE cell composition further comprises one or more of: a sugar acid, a base, an antioxidant, a halide salt, a basic salt, a phosphate salt, a sugar, a sugar alcohol, and water. 
     
     
         99 . The method of  claim 98 , wherein the sugar acid comprises lactobionic acid, glyceric acid, xylonic acid, gluconic acid, ascorbic acid, neuraminic acid, ketodeoxyoctulosonic acid, glucuronic acid, galacturonic acid, galacturonic acid, iduronic acid, tartaric acid, mucic acid, or saccharic acid. 
     
     
         100 . The method of  claim 98 , wherein the base comprises sodium hydroxide, or potassium hydroxide. 
     
     
         101 . The method of  claim 98 , wherein the antioxidant comprises L-glutathione, ascorbic acid, lipoic acid, uric acid, a carotene, alpha-tocopherol, or ubiquinol. 
     
     
         102 . The method of  claim 98 , wherein the halide salt comprises potassium chloride, sodium chloride, or magnesium chloride. 
     
     
         103 . The method of  claim 98 , wherein the basic salt comprises potassium bicarbonate, sodium bicarbonate, or sodium acetate. 
     
     
         104 . The method of  claim 98 , wherein the phosphate salt comprises potassium phosphate, sodium phosphate, or potassium phosphate. 
     
     
         105 . The method of  claim 98 , wherein the one or more sugars comprises dextrose, sucrose. 
     
     
         106 . The method of  claim 98 , wherein the sugar alcohol comprises mannitol, sorbitol, erythritol or xylitol. 
     
     
         107 . The method of  claim 82 , wherein the RPE cell composition comprises: adenosine, dextran-40, lactobionic acid, HEPES (N-(2-Hydroxyethyl) piperazine-N′-(2-ethanesulfonic acid)), sodium hydroxide, L-glutathione, potassium chloride, potassium bicarbonate, potassium phosphate, dextrose, sucrose, mannitol, calcium chloride, magnesium chloride, potassium hydroxide, sodium hydroxide, dimethyl sulfoxide (DMSO), and water. 
     
     
         108 . The method of  claim 82 , wherein at least about 60% to about 75%, or at least about 60% to about 92%, or at least about 60% to about 95%, or at least about 62% to about 70% of the cells are viable after thawing, alternatively, wherein at least about 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% of the cells are viable after thawing.