Cell repopulated collagen matrix for soft tissue repair and regeneration

Abstract

The present invention provides compositions for treating soft tissue injuries comprising a collagen matrix and mesenchymal stem cells adhered to the collagen matrix. Methods of making and using compositions comprising a collagen matrix and mesenchymal stem cells adhered to the collagen matrix are also provided.

1 . A composition for treating a soft tissue injury in a subject, the composition comprising:
 a collagen matrix, and   mesenchymal stem cells adhered to the collagen matrix, wherein the mesenchymal stem cells are derived from a tissue processed to form a cell suspension comprising mesenchymal stem cells and non-mesenchymal stem cells that is seeded onto the collagen matrix, and wherein the mesenchymal stem cells are not cultured ex vivo after formation of the cell suspension and prior to seeding of the cell suspension on the collagen matrix.   
     
     
         2 . The composition of  claim 1 , wherein the collagen matrix is skin, dermis, tendon, ligament, muscle, amnion, meniscus, small intestine submucosa, or bladder. 
     
     
         3 . The composition of  claim 1 , wherein the collagen matrix is treated to reduce immunogenicity. 
     
     
         4 - 6 . (canceled) 
     
     
         7 . The composition of  claim 3 , wherein the treated collagen matrix retains bioactive cytokines. 
     
     
         8 . (canceled) 
     
     
         9 . The composition of  claim 3 , wherein the treated collagen matrix retains bioactive growth factors. 
     
     
         10 . (canceled) 
     
     
         11 . The composition of  claim 1 , wherein the collagen matrix is decellularized dermis. 
     
     
         12 . The composition of  claim 1 , wherein the collagen matrix is dermis from which the epidermis layer has been removed. 
     
     
         13 . The composition of  claim 1 , wherein the collagen matrix is human, porcine, bovine, or equine. 
     
     
         14 . The composition of  claim 1 , wherein the tissue that is processed to form the cell suspension is selected from adipose tissue, muscle tissue, birth tissue, skin tissue, bone tissue, or bone marrow tissue. 
     
     
         15 - 20 . (canceled) 
     
     
         21 . The composition of  claim 1 , wherein the mesenchymal stem cells seeded on the collagen matrix express one or more positive mesenchymal stem cell markers. 
     
     
         22 . (canceled) 
     
     
         23 . A method of treating a soft tissue injury in a subject, the method comprising contacting the composition of  claim 1  to the site of the soft tissue injury. 
     
     
         24 . The method of  claim 23 , wherein the soft tissue injury is an injury to a tendon tissue, a ligament tissue, a meniscus tissue, a muscle tissue, a skin tissue, a bladder tissue, or a dermal tissue. 
     
     
         25 - 30 . (canceled) 
     
     
         31 . A method of making a composition for treating a soft tissue injury, the method comprising:
 (a) digesting a tissue to form a cell suspension comprising mesenchymal stem cells and non-mesenchymal stem cells;   (b) seeding the cell suspension onto a collagen matrix;   (c) incubating the collagen matrix seeded with the cell suspension under conditions suitable for adhering the mesenchymal stem cells to the collagen matrix; and   (d) removing the non-adherent cells from the collagen matrix.   
     
     
         32 . The method of  claim 31 , wherein the collagen matrix is skin, dermis, tendon, ligament, muscle, amnion, meniscus, small intestine submucosa, or bladder. 
     
     
         33 . The method of  claim 31 , wherein prior to step (b), the method further comprises treating the collagen matrix to reduce immunogenicity. 
     
     
         34 - 37 . (canceled) 
     
     
         38 . The method of  claim 33 , wherein the treated collagen matrix is non-immunogenic. 
     
     
         39 . The method of  claim 33 , wherein the treated collagen matrix retains bioactive cytokines. 
     
     
         40 . (canceled) 
     
     
         41 . The method of  claim 33 , wherein the treated collagen matrix retains bioactive growth factors. 
     
     
         42 . (canceled) 
     
     
         43 . The method of  claim 31 , wherein the collagen matrix is human, porcine, bovine, or equine. 
     
     
         44 . The method of  claim 31 , wherein the tissue that is digested to form the cell suspension is selected from adipose tissue, muscle tissue, birth tissue, skin tissue, bone tissue, or bone marrow tissue. 
     
     
         45 - 51 . (canceled)