60 / 2018-07-28 11:18:54

Construction of human liver tissue by bioprinting of embryonic stem cells and progenitor cells

biofabrication; stem cells; liver tissue

全体主题 > iii. Engineering tissues and organs in vitro and in vivo

The need for models that recapitulate natural human liver physiology is urgent for drug testing and development, study of liver disease mechanism and bioartificial liver applications. Hepatic progenitor cells and human embryonic stem cells are important cell sources for generating human hepatocytes when properly differentiated, which constitutes an efficient surrogate of liver function. However, the efficient and directed differentiation of stem cells towards mature hepatocytes still poses a great challenge. In recent years, a serial of research was conducted in our group: (1) we make the first attempt to bioplotting hepatic progenitor cell-laden hydrogel into 3D structure with the consideration of the time frame of bioprinting as well as differentiation; (2) off-the-shelf micro-stencil arrays are developed to generate adherent multilayered colonies composed of hESCs-derived cells. Uninterrupted cellular differentiation and proliferation is achieved to recapitulate the continuous and multi-stage liver development. Compared with conventional 2D format, biofabrication of hESCs and hepatic progenitor cells into 3D cellular construct facilitated efficient, directed and uniform differentiation of stem cells towards hepatocytes, and even liver tissue-like structure. In summary, liver-like tissues with tunable phenotype and function, i.e. hepatic tissue with bile duct network, hepatic tissue with tissue-relevent cell density, hepatic tissue with functional and evenly distributed single hepatocytes, were obtained. These work represent the potential of advanced 3D bioprinting systems in fabricating of human liver tissues with functional and developmental complexity.