Cartilage engineering: a crucial combination of cells, biomaterials and biofactors.

Injuries to articular cartilage are one of the most challenging issues of musculoskeletal medicine due to the poor intrinsic ability of this tissue for repair. The lack of efficient modalities of treatment has prompted research into tissue engineering combining chondrogenic cells, scaffold materials and environmental factors. The aim of this review is to focus on the recent advances made in exploiting the potential of biomaterial-assisted cell therapy for cartilage engineering. We discuss the requirements for identifying additional specific growth factors and evaluating the optimal combination of cells, growth factors and scaffolds that is able to respond to the functional demand placed upon cartilage tissue replacement in clinics. Finally, some of the major obstacles encountered in cartilage engineering are discussed, as well as future trends in clinical applications.

Multipotent mesenchymal stromal cells in articular diseases.

Although cartilage defects are common features of osteoarthritis and rheumatoid arthritis, current treatments can rarely restore the full function of native cartilage. Recent studies have provided new perspectives for cartilage engineering using multipotent mesenchymal stromal cells (MSC). Moreover, MSC have been used as immunosuppressant agents in autoimmune diseases and have tested successfully in animal models of arthritis. However, the sequential events occurring during chondrogenesis must be fully understood before we can reproduce the complex molecular events that lead to MSC differentiation and long-term maintenance of cartilage characteristics in the context of chronic joint inflammation. This chapter focuses on the potential of MSC to repair cartilage, with an emphasis on the factors that are known to be required in inducing chondrogenesis and on their immunosuppressive potential.

Multipotent mesenchymal stromal cells and immune tolerance.

Multipotent mesenchymal stromal cells or mesenchymal stem cells (MSC) are isolated mainly from bone marrow and adipose tissue but are identified in other tissues such as synovium, periosteum or placenta. They are characterised by their property to adhere to plastic, their phenotype and their ability to differentiate into three lineages (chondrocytes, osteoblasts and adipocytes). More recently, these cells were shown to escape immune recognition and inhibit immune responses. MSC may modulate the function of the major immune cell populations, including antigen-presenting cells, T cells, B cells and natural killer cells. The aim of this review is to focus on the molecular mechanisms, still poorly understood, which are responsible of the immunosuppressive effects mediated by the MSC. Finally, the data obtained from in vivo experimentation in various animal models as well as potential therapeutic applications will be presented.

Gene expression profile of multipotent mesenchymal stromal cells: Identification of pathways common to TGFbeta3/BMP2-induced chondrogenesis.

Multipotent mesenchymal stromal cells (MSC) display a high potential for the development of novel treatment strategies for cartilage repair. However, the pathways involved in their differentiation to functional non hypertrophic chondrocytes remain largely unknown, despite the work on embryologic development and the identification of key growth factors including TGFbeta, Hh, Wnt and FGF. In this study, we asked if we could identify specific biological networks common to the growth factors used (TGFbeta3 or BMP-2). To address this question, we used DNA microarrays and performed large-scale expression profiling of MSC at different time points during their chondrogenic differentiation. By comparing these data with those obtained during the differentiation of MSC into osteoblasts and adipocytes, we identified 318 genes specific for chondrogenesis and developed a new algorithm to classify the genes according to their kinetic profile. We distributed the selected genes in five classes according to their kinetic of expression. We could reconstruct three phases characterized by functional pathways. The first phase corresponds to cell attachment and apoptosis induction; the second phase is characterized by a proliferation/differentiation step, and the third phase is characterized by a differentiation/hypertrophy pathway. Indeed, these data propose new pathways to understand the complexity of MSC differentiation to chondrocytes.

Engineered mesenchymal stem cells for cartilage repair.

Healthy cartilage is a highly robust tissue, and is resilient against the stringent mechanical and biological constraints imposed upon it. Cartilage defects are common features of joint diseases, but current treatments can rarely restore the full function of native cartilage. Recent studies have provided new perspectives for cartilage engineering using mesenchymal stem cells (MSCs). However, the sequential events occurring during chondrogenesis must be fully understood before we are able to reproduce faithfully the complex molecular events that lead to MSC differentiation and long-term maintenance of cartilage characteristics. Here, we focus on the potential of MSCs to repair cartilage with an emphasis on the factors that are known to be required in inducing chondrogenesis.