In vitro reproduction of endochondral ossification using a 3D mesenchymal stem cell construct
Abstract
Endochondral ossification is one of the essential bone development processes in vertebrates. Although researchers from a variety of fields, including cellular/molecular biology, chemistry, and materials science, have worked to gain a better understanding of the tissue development, integration of findings from these different fields remains a major challenge. An in vitro model system that reproduces endochondral ossification would be a valuable tool for overcoming this problem, because an in vitro standardized model system can be easily accessed by researchers from different fields. Here, we fabricated a large 3D mesenchymal stem cell (MSC) construct with a ball-like morphology, which is termed a cell ball, and cultured it under a hypoxia condition, since hypoxia causes chondrogenic differentiation of MSCs in primordial cartilage, which is crucial for endochondral ossification. Region-specific chondrogenic differentiation of MSCs and mineralization within the cartilage tissue were observed in the cell ball. The precipitated