Mesenchymal stem cell-based therapies in regenerative medicine: applications in rheumatology

For several years, mesenchymal stem cells (MSCs; also called mesenchymal stromal cells) have been largely studied and used as a new therapeutic tool for a number of clinical applications, in particular for the treatment of rheumatologic disorders. MSCs indeed have therapeutic potential for bone and joint diseases due to their multipotent differentiation abilities and the secretion of a variety of cytokines and growth factors that confer on them anti-fibrotic, anti-apoptotic, pro-angiogenic and immunosuppressive properties. They are currently being tested in several clinical trials for such diverse applications as osteoarthritis, osteogenesis imperfecta, articular cartilage defects, osteonecrosis and bone fracture. More-over, good manufacturing practices for the production of clinical-grade MSCs at high expansion rates without transformation are now well established [1]. Here, we review the present knowledge on the mechanisms underlying the therapeutic properties of MSCs and their applications in animal models and clinics in the fields of bone and cartilage repair, chronic inflammatory or degenerative disorders, as well as genetic diseases.MSCs were first identified in the bone marrow (BM) [2] but are now described to reside in connective tissues and notably in adipose tissue (AT) [3], placenta [4], umbilical cord [5], dental pulp [6], tendon [7], trabecular bone [8] and synovium [9]. It has also been suggested that MSCs could reside in virtually all post-natal organs and tissues[10]. BM and AT are, however, the two main sources of MSCs for cell therapy due to high expansion potential and reproducible isolation procedures. Historically, the first characterized MSCs derived from BM remain the most intensively studied and are still the reference. AT-derived MSCs (ASCs) are easier to isolate in high numbers. Nevertheless, while they display characteristics similar to BM-MSCs, their transcriptomic and proteomic profiles show specificities particular to the tissue origin