Advances in Adult Stem Cell Differentiation and Cellular Reprogramming to Enhance Chondrogenesis

Abstract

Cell-based therapies to treat articular cartilage and osteochondral defects as a result of osteoarthritis or traumatic injury are a promising approach. Traditional sources of cells have been autologous chondrocytes which are culture expanded and implanted; however, dedifferentiation of these cells results in a type of fibrocartilage which has reduced therapeutic benefit. Advances in cellular reprogramming technology are either through generation of induced pluripotent stem cells (iPSCs) and subsequent chondrogenic or through direct reprogramming of adult cells to chondrocytes. These approaches have the potential to provide an unlimited source of cartilage for therapeutic applications; however, challenges remain in terms of efficient cellular differentiation and ability to integrate and repair tissues. Growth factor-based strategies previously used in chondrogenic differentiation of adult stem cells and embryonic stem cells have been successfully applied to induced pluripotent stem cells, enhancing the ability of iPSCs to produce both patient-specific chondrocytes and to produce large quantities of these cells. A combination of novel biomaterials and additive bioprinting have also opened new approaches to recapitulate zonal cartilage structure and repair of osteochondral defects. The development of innovative protocols to generate chondrocytes from a variety of primary cells continues to proceed rapidly, allowing fine tuning of differentiation processes to produce an articular cartilage phenotype with improved mechanical and tissue integration capabilities.