Pluripotent stem cell-derived oliogodendrocyte progenitor cells for the treatment of spinal cord injury

Abstract

The present disclosure provides methods and compositions for making and using pluripotent stem cell-derived oligodendrocyte progenitor cells.

What is claimed is: 
     
         1 . A method of reducing spinal cord injury-induced parenchymal cavitation in a human subject with an acute spinal cord injury, the method comprising directly injecting into the spinal cord injury site of said subject a composition comprising human pluripotent stem cell-derived oligodendrocyte progenitor cells (OPCs) that are capable of engrafting at a spinal cord injury site. 
     
     
         2 . The method according to  claim 1 , wherein administering the composition comprises directly injecting the composition into the spinal cord injury site approximately 5 mm caudal of the spinal cord injury epicenter. 
     
     
         3 . The method according to  claim 1 , further comprising administering to the subject a low dose immunosuppressant regimen. 
     
     
         4 . The method according to  claim 3 , wherein the immunosuppressant regimen comprises a tacrolimus dose of about 0.03 mg/kg/day per os, adjusted to maintain a trough blood concentration of about 3-7 ng/mL through about day 46 following the administering of the composition comprising a population of human pluripotent stem cell-derived OPCs, followed by tapering off and discontinuing the immunosuppressant regimen at about day 60 following the administering of the composition. 
     
     
         5 . The method according to  claim 1 , wherein the OPCs are capable of remaining within the spinal cord injury site of said subject for a period of about 180 days or longer following the administration of the composition to the spinal cord injury site. 
     
     
         6 . The method according to  claim 1 , wherein the OPCs are capable of remaining within the spinal cord injury site of said subject for a period of about 2 years or longer following the administration of the composition to the spinal cord injury site. 
     
     
         7 . The method according to  claim 1 , wherein the OPCs are capable of forming a tissue matrix in the spinal cord injury site of said subject within about 180 days or less, thereby reducing spinal cord injury-induced parenchymal cavitation. 
     
     
         8 . The method according to  claim 1 , wherein the subject has a thoracic or cervical spinal cord injury. 
     
     
         9 . The method according to  claim 1 , wherein the composition comprises between about 2×10 6  and about 50×10 6  cells. 
     
     
         10 . A method of inducing myelin repair or remyelination in a subject comprising administering a therapeutically effective amount of a composition comprising a population of human pluripotent stem cell-derived oligodendrocyte progenitor cells (OPCs) capable of secreting MCP-1 and one or more factors selected from Clusterin, ApoE, TIMP1 and TIMP2; wherein the OPCs are capable of reducing spinal cord injury-induced parenchymal cavitation in a human subject when injected into the spinal cord injury site. 
     
     
         11 . The method of  claim 10 , wherein the OPCs are injected into the spinal cord injury site approximately 5 mm caudal of the spinal cord injury epicenter of said subject. 
     
     
         12 . The method of  claim 10 , wherein said OPCs are capable of engrafting at said spinal cord injury site of said subject following implantation of a dose of the composition into said spinal cord injury site; and remaining within said spinal cord injury site for a period of 180 days or longer. 
     
     
         13 . The method according to  claim 10 , further comprising treating the subject to reduce immune rejection of the OPCs. 
     
     
         14 . The method according to  claim 10 , further comprising administering an anti-inflammatory agent to the subject. 
     
     
         15 . The method according to  claim 10 , wherein the subject has been diagnosed with a disease or pathology selected from: multiple sclerosis, leukodystrophy, Guillain-Barre Syndrome, Charcot-Marie-Tooth neuropathy, Tay-Sachs disease, Niemann-Pick disease, Gaucher disease, and Hurler Syndrome. 
     
     
         16 . The method according to  claim 10 , wherein the subject has been diagnosed with a condition selected from inflammation, stroke, immune disorders, metabolic disorders, and nutritional deficiencies. 
     
     
         17 . The method according to  claim 10 , wherein the subject has suffered a traumatic injury resulting in a loss of myelination. 
     
     
         18 . The method according to  claim 17 , wherein the traumatic injury is an acute spinal cord injury. 
     
     
         19 . The method according to  claim 17 , wherein the traumatic injury is cervical spinal cord injury. 
     
     
         20 . The method according to  claim 17 , wherein the traumatic injury is thoracic spinal cord injury.