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.

Description

FIELD OF THE INVENTION [0001] The present invention relates to compositions comprising bone marrow cells (BMC) and demineralized and / or mineralized bone matrix (DBM and MBM, respectively) and to their novel uses in induction of new bone and cartilage formation in mammals. BACKGROUND OF THE INVENTION [0002] New bone formation, such as in the case of damage repair or substitution of a removed part of the bone in postnatal mammals, can only occur in the presence of the following three essential components, (i) mesenchymal progenitor cells; (ii) a conductive scaffold for these cells to infiltrate and populate; and (iii) Bone Morphogenetic Proteins. Unfortunately, local conditions usually do not satisfy the requirements of osteogenesis, and thus substitution of removed, damaged or destroyed bones does not occur spontaneously. [0003] Previous research has already uncovered somewhat about these three components. [0004] It was shown that multipotent mesenchymal stem cells, which are capable...

AI Technical Summary

Benefits of technology

[0052] (g) cryogenic means for handling and maintaining BMC or BMC together with DBM.

Problems solved by technology

Unfortunately, local conditions usually do not satisfy the requirements of osteogenesis, and thus substitution of removed, damaged or destroyed bones does not occur spontaneously.

Each of these methods has limitations and disadvantages and most of them are expensive, cumbersome, innefective and rather impractical.

Autologous osteochondral graft is restricted to a small area of damaged cartilage, up to 2 cm2, and could cause discomfort, infection and morbidity in the donor site.

Allogeneic osteochondral graft is immunogenic, hence requires life-long use of undesired, hazardous immunosuppressive agents, which would be an impractical approach for routine orthopedic practice.

Transplantation of cultured chondrocytes is cumbersome and very expensive, involving a two-stage procedure.

Hence, adequate restoration of cartilage remains an unsolved problem.

However, the use of autografts has limitations, such as donor site discomfort, infection and morbidity and limited sizes and shapes of available grafts.

Even if enough tissue is transplanted there is an acute limitation in the number of mesenchymal stem cells with high proliferative potential present in the differentiated bone tissue implanted.

So far, most of the matrices that were tried in combined cell-matrix grafts were either immunogenic or non-biodegradable, and the remaining others did not possess conductive or inductive properties needed to support formation of biomechanical strong cartilage.

Cells used in combined cell-matrix grafts were in most of the cases chondrocytes, which were already fully differentiated cells, with relatively low metabolic activity and limited self-renewal capacity.

Whereas the proliferative capacity of such cells may be sufficient to maintain healthy cartilage, it is certainly insufficient for the development de novo of large areas of hyaline cartilage.

In addition to being immunogenic, mesenchymal progenitor cell allografts were not combined with optimal supportive matrix.

Thus, unfortunately, none of the available options fulfill all basic requirements, and all options are far from being satisfactory for reliable routine clinical application.

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