The Chinese University of Hong Kong (CUHK), Hong Kong
Abstract: For decades, the treatment of end-stage liver diseases has been hampered with donor liver shortage. Stem cell therapy can potentially overcome the limitation by supplying functional hepatocytes for cell therapy and tissue engineering. For example, the transplantation of human embryonic pluripotent stem cells (hESCs)-differentiated functional hepatocyte-like cells (HLCs) can contribute to liver regeneration by restoring damaged liver tissues. This can alleviate donor shortage burdens for liver transplantation treatments. However, many of the protocols available currently tends to be time and cost-consuming. Besides, these differentiated cells still possess an immature and heterogenous phenotype compared to primary human hepatocytes with low cell yields. In this study, we have differentiated hESCs in 2D monolayers, 3D spheroids, and microspheres, into HLCs utilizing human hepatic growth factors and Oncostatin M molecules. These cells were evaluated for their differentiation and maturation efficiency. Our present data demonstrated that, with our established protocol, these ESCs have been differentiated into HLCs with progressively maturing characteristics. An ESC-hepatocyte differentiation platform has then been established as a foundation for future explorations.