Stimulations and modulations of chondrogenic differentiation of human embryonic stem cells

Abstract

By using human embryonic stem cells (hESCs) as the model system, this study aims to understand the full span process of chondrogenesis, and how this process could be regulated by growth factors BMP2 and/or TGFI?1 in a controlled context both in vitro and in vivo. By culturing hESCs in 2-D EB monolayer and 3-D high-density micromass systems, BMP2 was shown to induce chondrogenic differentiation and maturation/hypertrophy, of which distinct temporal pattern differences were observed. Further analysis suggested that BMP2 probably exerts a bipotent effect in inducing both chondrogenic and osteogenic differentiation, while TGFI?1 played a steering effect in driving chondrogenesis predominately, with inhibition of osteogenesis. Both factors revealed little synergistic cooperation in enhancing chondrogenic differentiation, as compared to TGFI?1 alone. When these hEB-derived chondrogenic cells derived from growth factor pretreatment were implanted ectopically in SCID mice, TGFI?1-pretreated cells demonstrated maximum cartilage formation. Conversely, BMP2-pretreated cells showed minimum cartilage formation, possibly due to predominating osteogenic differentiation of hEB-derived cells.