Compositions comprising bone marrow cells together with demineralized and/or mineralized bone matrix and uses thereof in the induction of bone and cartilage formation

Abstract

A composition comprising bone marrow cells (BMC) and demineralized bone matrix (DBM) and/or mineralized bone matrix (MBM) and optionally comprising bone morphogenetic protein/s (BMP) and/or other active agents, particularly for use in the transplantation of mesenchymal progenitor cells into a joint and/or a cranio-facial maxillary bone, for restoring and/or enhancing the formation of a new hyaline cartilage and subchondral bone structure. The composition of the invention and method of treatment employing the same may be used for the treatment of hereditary or acquired bone disorders, hereditary or acquired cartilage disorders, malignant bone or cartilage disorders, metabolic bone diseases, bone infections, conditions involving bone or cartilage deformities and Paget's disease. The composition and method may further be used for the correction of complex fractures, bone replacement and formation of new bone in plastic or sexual surgery, for support of implants of joints, cranio-facial-maxillary bones, or other musculoskeletal implants, including artificial implants. The method of the invention may further be used for treating damaged joints or degenerative arthropathy associated with malformation and/or dysfunction of cartilage and/or subchondral bone. A kit is provided for performing transplantation into a joint or a cranio-facial-maxillary bone of a mammal of the composition of the invention.

1 - 45 . (canceled)  
   
   
       46 . A mixture comprising bone marrow cells (BMC) and demineralized bone matrix (DBM) and/or mineralized bone matrix (MBM) for use as a graft of mesenchymal progenitor cells for transplantation into a joint and/or a cranio-facial-maxillary bone of a subject in need.  
   
   
       47 . The mixture according to  claim 46 , wherein said BMC are allogeneic or said subject's own.  
   
   
       48 . The mixture according to  claim 46 , further comprising active agents, preferably selected from bone morphogenetic proteins (BMPs), immunosuppressants, immunomodulators, antibiotics and anti-inflammatory agents.  
   
   
       49 . A mixture according to  claim 46 , wherein the DBM and/or MBM are of vertebrate origin.  
   
   
       50 . The mixture according to  claim 46 , wherein the DBM and/or MBM are of human origin.  
   
   
       51 . The mixture according to  claim 46 , wherein the DBM or MBM are in powder or slice form.  
   
   
       52 . The mixture according to  claim 46 , wherein the particle size of the DBM is about 50 to 2500u.  
   
   
       53 . The mixture according to  claim 52 , wherein the particle size of the DBM is about 250 to 500u.  
   
   
       54 . The mixture according to  claim 46 , wherein the ratio between BMC and DBM is between 1:1 and 20:1 (volume:volume).  
   
   
       55 . The mixture according to  claim 54 , wherein the ratio between BMC and DBM is between 2:1 and 9:1 (volume:volume).  
   
   
       56 . The mixture according to  claim 55 , wherein the ratio between BMC and DBM is 4:1 (volume:volume).  
   
   
       57 . The mixture according to  claim 46 , wherein the subject is a human.  
   
   
       58 . The mixture according to  claim 55 , wherein the number of bone marrow cells in the mixture is from about 10 6  to 10 8  cells/ml.  
   
   
       59 . The mixture according to  claim 46 , further comprising a pharmaceutically acceptable carrier or diluent.  
   
   
       60 . A method for treating a patient suffering from a damaged joint, degenerative arthropathy, a hereditary or acquired bone disorder, hereditary or acquired cartilage disorder, a malignant bone or cartilage disorder, metabolic bone diseases, bone infections, conditions involving bone or cartilage deformities, or Paget's disease, comprising administering to the patient the mixture of  claim 46 .  
   
   
       61 . A method for transplantation of a mixture comprising BMC with DBM and/or MBM and optionally further comprising pharmaceutically acceptable carrier or diluent, into a joint or a cranio-facial-maxillary bone of a subject in need, wherein said method comprises introducing into said joint or bone a mixture as defined in  claim 46 .  
   
   
       62 . The method according to  claim 61 , wherein said mixture is administered non-invasively by a syringe, an arthroscopic procedure or by open surgery into the site of implantation.  
   
   
       63 . The method according to  claim 62 , for support of implants of joints, cranio-facial-maxillary bones, or other musculoskeletal implants.  
   
   
       64 . A method of treating a damaged joint or degenerative arthropathy associated with malformation and/or dysfunction of cartilage and/or subchondral bone in a mammal in need of such treatment, comprising administering into an affected joint or bone of said mammal a mixture comprising BMC with DBM and/or MBM, said mixture optionally further comprising a pharmaceutically acceptable carrier or diluent and/or additional active agents.  
   
   
       65 . The method according to  claim 64 , wherein the BMC are either allogeneic or said mammal's own.  
   
   
       66 . The method according to  claim 64 , wherein said DBM or MBM are in a slice, powder, gel, semi-solid or solid form embedded in or encapsulated in polymeric or biodegradable materials.  
   
   
       67 . The method according to  claim 66 , wherein the particle size of said DBM is about 50 to 2500u.  
   
   
       68 . The method according to  claim 67 , wherein the particle size of said DBM is about 250 to 500u.  
   
   
       69 . The method according to  claim 64 , wherein the ratio between the transplanted BMC and DBM is between 1:1 and 20:1 (volume:volume).  
   
   
       70 . The method according to  claim 69 , wherein the ratio between the transplanted BMC and DBM is between 2:1 and 9:1 (volume:volume).  
   
   
       71 . The method according to  claim 70 , wherein the ratio between the transplanted BMC and DBM is 4:1 (volume:volume).  
   
   
       72 . A non-invasive implantation method for support of implants of joints or other musculoskeletal implants, comprising introducing a graft into a joint or a cranio-facial-maxillary bone of a subject in need, wherein said graft comprises the mixture of  claim 46 .  
   
   
       73 . A kit for performing transplantation into a joint or a cranio-facial-maxillary bone of a mammal of a mixture as defined in  claim 46 , wherein said kit comprises: 
 (a) the mixture-as defined in  claim 46;     (b) a BM aspiration needle;    (c) an intra-osseous bone drilling burr;    (d) a needle with a thick lumen for infusion of viscous bone marrow-DBM mixture;    (e) a 2-way lumen connector for simultaneous mixing of BMC-DBM and diluent;    (f) a medium for maintaining BMC; and optionally    (g) cryogenic means for handling and maintaining BMC or BMC together with DBM.    
   
   
       74 . The kit according to  claim 73 , optionally further comprising a carrier and/or diluent for the mixture.