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In addition, current therapies are not specifically directed toward basic mechanisms of muscle cell repair and regeneration.Īccordingly, there exists a need for methods and compositions that can induce muscle repair and regeneration speedily and effectively. These therapies can provide some beneficial outcomes, but are far from ideal in terms of effectiveness and efficiency. Current therapies include massage, ultrasound, hyperbaric oxygen delivery, and drug treatments such as fenoterol and insulin-like growth factor-1. In such cases, the muscles lose function and strength of contraction and can be replaced by scar tissue (connective tissue) that by lacking contractility, causes loss of muscle function. In general, muscles have adequate repair capacity particularly in young people, but this repair process can become ineffective in older people or after repeated rounds of over-use, severe trauma or other processes. Skeletal muscles can become injured for a variety of reasons including over-use, trauma, infections and loss of blood circulation. These injuries may cause tremendous pain and can incapacitate the affected person, preventing them from being able to go to work or even to participate in normal daily activities. Injuries to muscles include acute injuries to skeletal muscles such as contusions (bruises), lacerations, ischemia, strains, and complete ruptures. The present invention relates to methods and compositions for muscle repair and regeneration. The government has certain rights in this invention. W81XWH-07-1-0212 awarded by the United States Army. This invention was made with government support under Grant No. 1, 2010, the contents of which are incorporated herein by reference in their entirety.
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This application claims the benefit of 35 U.S.C. The method of claim 2, wherein the injured muscle is the result of muscle atrophy/wasting. The method of claim 2, wherein the injured muscle tissue is dystrophic muscle or an ageing muscle.ġ7. The method of claim 2, wherein the injured muscle results from physical injury or accident, disease, infection, over-use, loss of blood circulation, or muscle atrophy or wasting.ġ6. The method of claim 2, wherein the RARγ agonist is selected from the group consisting of CD-271 (6-(4-Methoxy-3-tricyclodec-1-ylphenyl)-2-naphthalenecarboxylic acid) CD-394, CD-1530 (4-(6-Hydroxy-7-tricyclodec-1-yl-2-naphthalenyl)benzoic acid) CD-2247 BMS-270394 (3-Fluoro-4-benzoic acid) BMS-189961 (3-Fluoro-4-benzoic acid) CH-55 (4-benzoic acid) 6-naphthalene-2-carboxylic acid 5-thiophene-2-carboxylic acid and enantiomers, derivatives, prodrugs, and pharmaceutically acceptable salts thereof.ġ5. The method of claim 2, further comprising administering an antiinflammatory agent to the subject.ġ4. The method of claim 2, wherein the pluripotent stem cells are human.ġ3. The method of claim 2, wherein the mesenchymal stem cells are mammalian.ġ2. The method of claim 2, wherein the mesenchymal stem cells are autologous or heterologous to the subject.ġ1. The method of claim 2, wherein the administering is by transplantation of the cells into the subject.ġ0. The method of claim 2, wherein the administering is local.ĩ. The method of claim 2, wherein the pre-treated stem cells have been pre-treated with the RARγ agonist for a period of about 3 days.Ĩ. The method of claim 5, wherein the pre-treated stem cells and non-treated stem cells are administered at a ratio of 1:1.ħ. The method of claim 2, wherein the pre-treated stem cells are administered in combination with non-treated stem cells.Ħ. The method of claim 3, wherein the compound tissue injury comprises an injury to muscle and bone.ĥ. The method of claim 2, wherein the muscle injury is a compound tissue injury.Ĥ. A method of muscle repair or regeneration in a subject, comprising (i) providing pre-treated stem cells produced by contacting mesenchymal stem cells with an amount of a retinoic acid receptor gamma (RARγ) agonist effective to induce or stimulate myogenic differentiation and (ii) administering said pre-treated stem cells to a subject at a site of muscle injury to repair or regenerate muscle at the site.ģ. A method of muscle repair of regeneration in a subject, comprising orally administering a therapeutically effective amount of CD-271 (6-(4-Methoxy-3-tricyclodec-1-ylphenyl)-2-naphthalenecarboxylic acid) to a subject with damaged muscle tissue as a result of infection, wherein the administration is begun later than 3 days after incurrence of the damaged muscle tissue by the subject.Ģ.