Stem cell-produced microvesicles for treating tendon pathologies

Abstract

Microvesicles produced by stem cells grown on a silk scaffold for enhancing stem cell self-renewal/proliferation and promoting tenogenesis in damaged tendons, and their use in tendon wound repair and tendinopathy treatment. Also provided are compositions containing the microvesicles and devices for obtaining them.

1 - 35 . (canceled) 
     
     
         36 . A method of treating a damaged tendon in a first mammalian subject comprising:
 obtaining, or having obtained, an amount of mesenchymal stem cells from a subject of the same species as the first mammalian subject;   culturing the mesenchymal stem cells on a scaffold so as to produce vesicles; and   administering to the first mammalian subject an amount of the vesicles effective to treat a damaged tendon,   or   a method of differentiating stem cells into a tendon lineage by physical means comprising:   obtaining, or having obtained, an amount of mesenchymal stem cells from a mammalian subject;   culturing the mesenchymal stem cells on a scaffold comprising a 3D scaffold comprising a plurality of fibers substantially aligned in a parallel manner along their longitudinal axes and held under tension in a longitudinal direction of the fibers, so as to induce elongation of the mesenchymal stem cells and tendon lineage differentiation.   
     
     
         37 . The method of  claim 36 , wherein the vesicles have been secreted from the mesenchymal stem cells. 
     
     
         38 . The method of  claim 36 , wherein the mesenchymal stem cells have been cultured on the scaffold at P1 to P3. 
     
     
         39 . The method of  claim 36 , wherein the mesenchymal stem cells (MSC) are adipose-derived stem cells, bone marrow-derived stem cells, bursa-derived stem cells, or are tendon stem/progenitor cells. 
     
     
         40 . The method of  claim 36 , wherein the subject of the same species is the same subject that is being treated. 
     
     
         41 . The method of  claim 36 , wherein the damaged tendon is damaged as a result of a tendinopathy, a physical injury to the tendon, or is a ruptured tendon. 
     
     
         42 . The method of  claim 36 , wherein the amount of vesicles is administered locally into the tendon. 
     
     
         43 . The method of  claim 36 , wherein the amount of vesicles is administered by injection. 
     
     
         44 . The method of  claim 36 , wherein the amount of vesicles has been cryopreserved prior to administering them. 
     
     
         45 . The method of  claim 36 , wherein the scaffold is a 3D scaffold comprising a plurality of fibers substantially aligned in a parallel manner along their longitudinal axes and held under tension in a longitudinal direction of the fibers. 
     
     
         46 . The method of  claim 39 , wherein the mesenchymal stem cells are adipose-derived stem cells. 
     
     
         47 . The method of  claim 46 , comprising obtaining the adipose-derived stem cells from the subject by cannula. 
     
     
         48 . The method of  claim 36 , wherein the vesicles comprise vesicles of 40 nm to 100 nm average diameter. 
     
     
         49 . A system comprising a 3D scaffold comprising a plurality of fibers substantially aligned in a parallel manner along their longitudinal axes and held under tension in a longitudinal direction of the fibers, and mesenchymal stem cells obtained from a mammalian subject present on the 3D scaffold, and vesicles derived from the mesenchymal stem cells. 
     
     
         50 . The system of  claim 49 , wherein the 3D scaffold is present in a sterile container. 
     
     
         51 . The system of  claim 49 , wherein the fibers have an average diameter of 11 uM to 15 uM. 
     
     
         52 . A composition comprising a sterile pharmaceutically acceptable carrier and an amount of vesicles derived from a supernatant of mesenchymal stem cells cultured on a 3D scaffold comprising a plurality of fibers substantially aligned in a parallel manner along their longitudinal axes and held under tension in a longitudinal direction of the fibers. 
     
     
         53 . The composition of  claim 52 , wherein the sterile pharmaceutically acceptable carrier comprises a buffer. 
     
     
         54 . The composition of  claim 52 , which is an injectable composition.