STEM CELL-PRODUCED MICROVESICLES FOR TREATING TENDON PATHOLOGIES
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.