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 . The method of  claim 82 , 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. 
     
     
         83 . 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. 
     
     
         84 . The method of  claim 82 , wherein the composition is frozen prior to administration. 
     
     
         85 . The method of  claim 82 , wherein the retinal condition comprises age related macular degeneration (AMD). 
     
     
         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 composition into a delivery device after thawing and prior to administration. 
     
     
         88 . The method of  claim 87 , wherein the delivery device comprises a needle. 
     
     
         89 . The method of  claim 82 , the composition comprising between about 0.5% and about 7% DMSO. 
     
     
         90 . The method of  claim 82 , the composition comprising between about 1.5% and about 6.5% DMSO. 
     
     
         91 . The method of  claim 82 , the composition comprising between about 1.5% and about 3% DMSO. 
     
     
         92 . The method of  claim 82 , the composition comprising between about 4% and about 6% DMSO. 
     
     
         93 . The method of  claim 82 , wherein the 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 composition prior to administration to the subject. 
     
     
         95 . The method of  claim 82 , wherein the 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. 
     
     
         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 composition is administered to the retina of the subject. 
     
     
         99 . The method of  claim 82 , wherein the retinal condition is a retinal degenerative disease. 
     
     
         100 . The method of  claim 99 , wherein the retinal degenerative disease comprises one or more of: RPE dysfunction, photoreceptor dysfunction, accumulation of lipofuscin, formation of drusen, or inflammation. 
     
     
         101 . The method of  claim 82 , wherein the composition is administered in the subretinal space. 
     
     
         102 . The method of  claim 82 , wherein the composition is injected. 
     
     
         103 . The method of  claim 82 , wherein the composition is administered as a single dose treatment. 
     
     
         104 . The method of  claim 82 , wherein the composition is administered without vitrectomy and without the need to pierce the retina. 
     
     
         105 . The method of  claim 82 , wherein the composition is administered by a suprachoroidal injection. 
     
     
         106 . The method of  claim 82 , wherein the 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. 
     
     
         107 . The method of  claim 82 , wherein the 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 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% of the cells are viable after thawing. 
     
     
         109 . 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);   b) storing the cell suspension at a cryopreservation temperature; and   c) thawing the cryopreserved suspension, wherein at least about 60% to about 92% of the cells are viable after thawing.