The role of cellular interactions in the induction of hepatocyte polarity and functional maturation in stem cell-derived hepatic cells.

The unique microenvironment found within the liver in vivo plays a key role in the induction of functional maturation in the developing hepatocyte. During organogenesis, hepatocytes acquire a polar phenotype that allows them to perform their functions of bile production and transport, protein synthesis, metabolism, and detoxification simultaneously, independently, and efficiently. It is thought that the induction of polarity and functional maturation in hepatocytes is dependent on the complex interplay of cell-cell and cell-extracellular matrix (ECM) interactions. While this process is highly efficient in the human liver, it has been shown that hepatocytes rapidly lose their functions when placed in cell culture. This poses a challenge for the development of a bioartificial liver (BAL) support system, which utilizes a live cellular source to perform hepatic functions in the event of acute liver failure or primary nonfunction. However, once the molecular mechanisms underlying the induction of hepatocyte polarity are fully identified, it will be possible to develop highly functional hepatic cells from human pluripotent stem cells (hPSCs). This new cell line would be an ideal cellular source for a BAL system, as it would have both the functionality and longevity to support a patient through the entire clinical course of treatment. In this review, we explore the literature that has examined the potential mechanisms that induce polarity in the developing hepatocyte and discuss the future implications of this knowledge in a clinical setting from a bioengineering perspective.

Clinical translation of bioartificial liver support systems with human pluripotent stem cell-derived hepatic cells.

There is currently a pressing need for alternative therapies to liver transplantation. The number of patients waiting for a liver transplant is substantially higher than the number of transplantable donor livers, resulting in a long waiting time and a high waiting list mortality. An extracorporeal liver support system is one possible approach to overcome this problem. However, the ideal cell source for developing bioartificial liver (BAL) support systems has yet to be determined. Recent advancements in stem cell technology allow researchers to generate highly functional hepatocyte-like cells from human pluripotent stem cells (hPSCs). In this mini-review, we summarize previous clinical trials with different BAL systems, and discuss advantages of and potential obstacles to utilizing hPSC-derived hepatic cells in clinical-scale BAL systems.