Compositions and Methods for Muscle Regeneration Using Prostaglandin E2

Abstract

Provided herein are compositions, methods, and kits for proliferating muscle cells by exposing the muscle cells to a prostaglandin E2 (PGE2) compound or compound that activates PGE2 signaling. Also provided are methods for regenerating muscle in a subject suffering from muscular atrophy, dystrophy, and/or injury by administering a PGE2 compound alone or in combination with isolated muscle cells. The PGE2 compound in combination with the isolated muscle cells can be administered prophylactically to prevent a muscle disease or condition.

1 - 30 . (canceled) 
     
     
         31 . A composition to increase a population of muscle cells in a subject, comprising prostaglandin E2 (PGE2), a PGE2 derivative, a PGE2 analog, a PGE2 prodrug, a PGE2 receptor agonist, a compound that attenuates PGE2 catabolism, a compound that neutralizes PGE2 inhibition, a salt thereof, or a combination thereof. 
     
     
         32 . The composition of  claim 31 , wherein the composition comprises PGE2 or a salt thereof. 
     
     
         33 . The composition of  claim 31 , wherein the composition is administered by oral administration, intramuscular administration, intradermal administration, subcutaneous administration, intravenous administration or a combination thereof. 
     
     
         34 . The composition of  claim 33 , wherein the composition is administered by intramuscular administration. 
     
     
         35 . The composition of  claim 31 , wherein the composition is administered by injection. 
     
     
         36 . The composition of  claim 31 , wherein the composition is administered by an acute exposure, an intermittent exposure, a chronic exposure, or a continuous exposure, to the subject. 
     
     
         37 . The composition of  claim 36 , wherein the composition is administered by an acute, intermittent, or continuous exposure. 
     
     
         38 . The composition of  claim 31 , wherein the population of muscle cells comprises muscle stem cells, satellite cells, muscle progenitor cells, myocytes, myoblast, myotubes, myofibers, or a combination thereof. 
     
     
         39 . The composition of  claim 38 , wherein the population of muscle cells comprises myogenic cells. 
     
     
         40 . The composition of  claim 39 , wherein the myogenic cells comprise stem cells, satellite cells, progenitor cells, or a combination thereof. 
     
     
         41 . The composition of  claim 31 , wherein the subject has muscle damage, muscle injury, muscle atrophy, or a combination thereof. 
     
     
         42 . The composition of  claim 41 , wherein the subject has acute muscle injury or trauma, soft tissue hand injury, or a combination thereof. 
     
     
         43 . The composition of  claim 31 , wherein an effective amount to increase the population of muscle cells of the composition is administered to the subject. 
     
     
         44 . The composition of  claim 31 , wherein the PGE2 analog comprises 2,2-difluoro-16-phenoxy-PGE2, 2-decarboxy-2-hydroxymethyl-16-fluoro-PGE2, 2-decarboxy-2-hydroxymethyl-11-deoxy-PGE2, 19(R)-hydroxy PGE2, 16,16-dimethyl PGE2 p-(p-acetamidobenamido) phenyl ester, 11-deoxy-16,16-dimethyl PGE2, 9-deoxy-9-methylene-16,16,-dimethyl PGE2, 9-deoxy-9-methylene PGE2, butaprost, sulprostone, enoprostil, PGE2 serinol amide, PGE2 methyl ester, 16-phenyl tetranor PGE2, 5-trans-PGE2, 15(S)-15-methyl PGE2, and 15(R)-15-methyl PGE2, or any combination thereof. 
     
     
         45 . The composition of  claim 31 , wherein the PGE2 receptor agonist is an agonist of EP1 receptor, EP2 receptor, EP3 receptor, EP4 receptor, or a combination thereof. 
     
     
         46 . The composition of  claim 45 , wherein the PGE2 receptor agonist is an agonist of EP4 receptor.