Differentiation of Hepatic Stellate Cells from Pluripotent Stem Cells

Hepatic stellate cells (HSCs) are non-parenchymal cells with a mesenchymal origin involved in vitamin A storage and extracellular matrix (ECM) homeostasis. In response to injury, HSCs activate and acquire myofibroblastic features, participating in the wound healing response. Upon chronic liver injury, HSCs become the main contributors to ECM deposition and to the progression of fibrosis. Due to their relevant roles in liver function and pathophysiology, it is of utmost importance to develop means to obtain HSCs for liver disease modeling and drug development. Here, we describe a directed differentiation protocol from human pluripotent stem cells (hPSCs) to obtain functional HSCs (PSC-HSCs). The procedure is based on the subsequent addition of growth factors during 12 days of differentiation. PSC-HSCs can be used for liver modeling and drug screening assays, hence emerging as a promising and reliable source of HSCs.