PROF. YAN-RU LOU

Differentiation of Human Pluripotent Stem Cells into Hepatic Cells

Human pluripotent stem cell (hPSC)-derived hepatocytes hold great potential in drug discovery and development, regenerative medicine, and disease modeling. By combining knowledge and techniques in developmental biology, tissue engineering, and material sciences, the in vitro differentiation of hPSCs into hepatocytes have advanced considerably in recent years. One of the current challenges is cell maturation. It is known that cell differentiation is mediated by not only the soluble factors, such as growth factors and cytokines, but also extracellular matrix (ECM). In addition, thyroid hormones during early development are shown to be important in organ development. Here we have studied the role of thyroid hormones and ECM in the hepatic differentiation of hPSCs at different stages. We found that laminin-511 and -521 promoted hepatic specification of hPSC-derived definitive endoderm cells. Thyroid hormones inhibited the expression of fetal liver marker and induced the expression of mature liver markers. In conclusion, we demonstrate that both thyroid hormones and laminins differentially regulate hepatic differentiation and maturation of hPSCs.