Protocol for Directed Differentiation of Human Induced Pluripotent Stem Cells (iPSCs) to a Hepatic Lineage

Directed differentiation is a powerful cell culture technique where developmental pathways are applied to a pluripotent progenitor in order to generate specific terminally differentiated cell populations. Here, we describe a serum-free protocol using growth factors in defined concentrations to derive iPSC-hepatic cells starting from both feeder and feeder-free conditions. The generated iPSC-hepatic cells are developmentally similar to fetal stage hepatocytes, and when generated from patients with genetic mutations such as alpha-1 antitrypsin deficiency recapitulate pathologic changes associated with clinical disease, such as protein misfolding, intracellular retention of misfolded proteins, and elevated levels of ER stress.