The invention relates to a method for producing
cartilage from pluripotent stem cells (PSCs), the method comprising providing chondrocytes by: 1) providing pluripotent stem cells (PSCs); 2) inducing differentiation of the PSCs into a primitive streak / mesendoderm by culturing the PSCs in hypoxic conditions, in a (mesendodermic) culture media comprising: i) a Wingless / Integrated (WNT) family member, ii) an Activin family member, and iii) a
Fibroblast Growth Factor (FGF) family member; 3) inducing differentiation of the primitive streak / mesendoderm into a
mesoderm by culturing the primitive streak / mesendoderm in hypoxic conditions, in a (mesodermic) culture media comprising: i) a FGF family member, ii) a
bone morphogenetic protein (BMP) family member, iii)
Follistatin, and iv) a
Neurotrophin (NT); and 4) inducing differentiation of the
mesoderm into chondrocytes by culturing the
mesoderm in hypoxic conditions, in a (chondroinductive) culture media comprising: i) a FGF family member, ii) a BMP family member, iii) a
Neurotrophin, and iv) a Growth / Differentiation Factor (GDF) family member; and forming a pellet of the chondrocytes and culturing the pellet of the chondrocytes in a culture media under hypoxic conditions to produce the
cartilage. The invention further relates to methods of
chondrocyte production, synthetically produced
cartilage, and use in therapy.