4.2.2. Cartilage Specific signature gene cluster regulation was seen during in vitro chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells which were immobilized in a self-gelling alginate hydrogel. Upregulation of transcription factor genes as well as a signature cluster of extracellular matrix genes occurred during chondrogenesis while gene clusters involved in immune response, blood vessel development, and cell adhesion were downregulated [95]. Marker genes identified in this study show that stem cells can be directed to produce hyaline cartilage when immobilized in 3D alginate hydrogels. Immobilizing cells with chondrogenic potential in an alginate hydrogel has shown that neocartilage can be formed by mesenchymal stem cells [137]. Here, production of not only type II collagen but also assembled fibrils was dependent on cell seeding density. When cells were seeded at a high density, fibril assembly and procollagen processing occurred at a distance from the cell surface.