Prevention and treatment of bone and cartilage damage or disease

Abstract

Compositions and methods for the prevention and/or treatment of conditions involving disease or damage in mammalian cartilage and bone, using mesenchymal stem cells isolated with anti-integrin α10 antibodies are disclosed.

1 .- 69 . (canceled) 
     
     
         70 . An enriched integrin α10 population of undifferentiated cells, wherein at least 60% of the cells of the population express integrin α10 subunit, wherein the cells are WWII negative and CD45 negative, and wherein the cells are selected from mesenchymal stem cells (MSCs), mesenchymal progenitor cells, and mesenchymal stromal cells. 
     
     
         71 . The enriched integrin α10 population of  claim 70 , wherein the cells are autologous or allogenic. 
     
     
         72 . The enriched integrin α10 population of  claim 70 , wherein at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% of the total cells comprised in the population express integrin α10 subunit. 
     
     
         73 . The enriched integrin α10 population of  claim 70 , wherein said population is an in vitro cell culture. 
     
     
         74 . The enriched integrin α10 population of  claim 70 , wherein the cells that express integrin α10 are isolated with an anti-integrin α10 antibody. 
     
     
         75 . The enriched integrin α10 population of  claim 74 , wherein the anti-integrin α10 antibody is a monoclonal antibody. 
     
     
         76 . The enriched integrin α10 population of  claim 70 , wherein the cells are derived from adipose tissue, bone marrow, synovial membrane, peripheral blood, cord blood, umbilical cord blood, Wharton's jelly, or amniotic fluid. 
     
     
         77 . The enriched integrin α10 population of  claim 70 , wherein the MSCs express CD44, CD90 and CD105. 
     
     
         78 . A method of delaying or stopping the onset of subchondral bone sclerosis, damage due to traumatic joint injuries, and/or degenerative joint disease (DJD) in a mammal in need thereof, comprising injecting a therapeutically effective amount of the enriched integrin α10 population of cells of  claim 70  into a damaged joint and/or bone of the mammal. 
     
     
         79 . The method of  claim 78 , wherein the degenerative joint disease (DJD) is selected from subchondral bone disease, cartilage degeneration, post-traumatic osteoarthritis, inflammatory arthritis, and congenital malformation and/or deformation of the musculoskeletal system, and wherein the damage due to traumatic joint injury is selected from osteochondral damage, tendon damage, ligament damage, and muscle damage. 
     
     
         80 . The method of  claim 79 , wherein the osteochondral damage comprises articular cartilage damage and/or bone damage. 
     
     
         81 . The method of  claim 79 , wherein the osteochondral damage, cartilage damage or injury is a break, sprain, bruise, tear, fracture, rupture, a cartilage fissure, a cartilage microfracture, a chondral defect, a tendon rupture, a ligament rupture, or a bone fracture, and/or wherein the osteochondral damage, cartilage damage or injury in the joint is in a muscle, tendon, bone, ligament, cartilage, or meniscus. 
     
     
         82 . The method of  claim 78 , wherein the population of cells comprise MSCs that are formulated into a cell aggregate prior to intra-articular injection. 
     
     
         83 . The method of  claim 78 , wherein the mammal is a human, horse, pony, ox, donkey, mule, camelid, cat, dog, pig, or cow. 
     
     
         84 . A method of manufacturing an enriched integrin α10 population of undifferentiated cells selected from mesenchymal stem cells (MSCs), mesenchymal progenitor cells, and mesenchymal stromal cells, wherein at least 60% of the cells of the population express integrin α10 subunit, the method comprising:
 (a) isolating a population of stem cells from adipose tissue, bone marrow, synovial membrane, cord blood, Wharton's jelly, or amniotic fluid; 
 (b) culturing the isolated cells in a plastic culture vessel; 
 (c) discarding non-adhered cells; 
 (d) inducing integrin α10 expression by adding culture media, wherein the culture media is a serum-free media or a media comprising mammalian serum, and wherein the culture media comprises platelet lysate; 
 (e) selecting the cells that express integrin α10, and 
 (f) expanding the selected cells, thereby producing an enriched integrin α10 population of undifferentiated cells selected from mesenchymal stem cells (MSCs), mesenchymal progenitor cells, and mesenchymal stromal cells. 
 
     
     
         85 . The method of  claim 84 , wherein the culture media in step (d) comprises fibroblast growth factor 2 (FGF2) and/or transforming growth factor beta (TGFβ).