Novel Mensenchymal Stem Cells And Bone-Forming Cells

Abstract

The invention relates to a new type of mesenchymal stem cells (MSC) which co-express at least one mesenchymal marker, preferably at least CD105 and CD34. Also provided are bone-forming cells having an analogous phenotype. The invention also provides the cells and cell populations, as well as further products comprising such and uses thereof in bone therapy.

1 - 23 . (canceled) 
     
     
         24 . A method for treating a bone-related disorder in a subject in need of such treatment, comprising administering to said subject a therapeutically or prophylactically effective amount of in vitro expanded mesenchymal stem cells (MSCs) originated from human bone marrow, wherein said in vitro expanded MSCs express surface markers comprising CD105 and CD34, and wherein at least 80% of the in vitro expanded MSCs further express surface markers CD90 and CD73. 
     
     
         25 . The method according to  claim 24 , wherein the in vitro expanded MSCs co-express CD105, CD90, CD73 and CD34. 
     
     
         26 . The method according to  claim 24 , wherein the in vitro expanded MSCs display both osteogenic properties and pro-angiogenic properties. 
     
     
         27 . The method according to  claim 24 , wherein the in vitro expanded MSCs are comprised in a cell population. 
     
     
         28 . The method according to  claim 24 , wherein the in vitro expanded MSCs are autologous, allogeneic, or xenogeneic to the subject. 
     
     
         29 . The method according to  claim 24 , wherein the in vitro expanded MSCs are allogeneic to the subject. 
     
     
         30 . The method according to  claim 24 , wherein the in vitro expanded MSCs are formulated in a pharmaceutical composition comprising one or more pharmaceutically acceptable carriers and/or excipients. 
     
     
         31 . The method according to  claim 30 , wherein the pharmaceutical composition comprises one or more further components useful in the repair of bone wounds and defects. 
     
     
         32 . The method according to  claim 31 , wherein said one or more further component is selected from the group consisting of bone morphogenetic proteins, bone matrix, hydroxyapatite/tricalcium phosphate particles (HA/TCP), granular ceramic, gelatine, poly-lactic acid, poly-lactic glycolic acid, hyaluronic acid, chitosan, poly-L-lysine, collagen, osteonectin, fibrinogen, and osteocalcin. 
     
     
         33 . The method according to  claim 32 , wherein the bone matrix is demineralised bone matrix (DBM). 
     
     
         34 . The method according to  claim 24 , wherein the in vitro expanded MSCs are administered in a form of a liquid composition. 
     
     
         35 . The method according to  claim 24 , wherein the in vitro expanded MSCs have been transferred to and/or cultured on a substrate to provide for an implant to be administered to the subject. 
     
     
         36 . The method according to  claim 35 , wherein the substrate is selected from metal, a bioactive surface, a polymer surface, or a siliceous material. 
     
     
         37 . The method according to  claim 36 , wherein the metal is titanium, cobalt/chromium alloy, or stainless steel. 
     
     
         38 . The method according to  claim 36 , wherein the bioactive surface is calcium phosphate. 
     
     
         39 . The method according to  claim 36 , wherein the polymer surface is polyethylene. 
     
     
         40 . The method according to  claim 36 , wherein the siliceous material is a glass ceramic. 
     
     
         41 . The method according to  claim 24 , wherein the in vitro expanded MSCs have been transferred to and/or cultured on a biocompatible three-dimensional solid support to provide for an implant to be administered to the subject. 
     
     
         42 . The method according to  claim 41 , wherein the biocompatible three-dimensional solid support is made of calcium carbonate, porous ceramics based on alumina, on zirconia, on tricalcium phosphate, and/or hydroxyapatite, or glass ceramics. 
     
     
         43 . The method according to  claim 24 , wherein the in vitro expanded MSCs are administered systemically, topically or at the site of a bone lesion. 
     
     
         44 . The method according to  claim 24 , wherein the subject is human. 
     
     
         45 . The method according to  claim 24 , wherein the bone-related disorder is a local or systemic disorder. 
     
     
         46 . The method according to  claim 24 , wherein the bone-related disorder is characterised by decreased bone formation or excessive bone resorption, by decreased number, viability or function of osteoblasts or osteocytes present in the bone, by decreased bone mass in a subject, by thinning of bone, or by compromised bone strength or elasticity. 
     
     
         47 . The method according to  claim 24 , wherein the bone-related disorder is selected from the group consisting of osteoporosis or osteopenia, any type of fracture, conditions requiring bone fusion, maxillo-facial fractures, bone reconstruction, cranio-facial bone reconstruction, osteogenesis imperfecta, osteolytic bone cancer, Paget's Disease, endocrinological disorders, hypophsophatemia, hypocalcemia, renal osteodystrophy, osteomalacia, adynamic bone disease, rheumatoid arthritis, hyperparathyroidism, primary hyperparathyroidism, secondary hyperparathyroidism, periodontal disease, Gorham-Stout disease, and McCune-Albright syndrome. 
     
     
         48 . The method according to  claim 47 , wherein the osteoporosis or osteopenia is primary, postmenopausal, senile, corticoid induced or any secondary, mono- or multisite osteonecrosis. 
     
     
         49 . The method according to  claim 47 , wherein the fracture is non-union, mal-union, delayed union fractures or compression. 
     
     
         50 . The method according to  claim 47 , wherein the condition requiring bone fusion is spinal fusion or rebuilding. 
     
     
         51 . The method according to  claim 47 , wherein the bone reconstruction is after traumatic injury or cancer surgery.