Pluripotent Stem Cells and Hepatocyte Development
Induced pluripotent stem cells can be routinely generated from easily accessible tissues, such as blood and skin, in a process of cellular reprogramming. They are easily grown, scalable, and can in a developmentally appropriate and efficient manner be differentiated towards the hepatocyte lineage. iPS derived hepatocyte-like cells not only express hepatocyte-specific markers but also have hepatocyte function, i.e. secrete serum proteins and have cytochrome P450 activity. However, current protocols fall short of producing a bonafide “adult” hepatocyte as iPS derived hepatocyte-like cells phenotype and function is more consistent with fetal hepatocytes. The current state of the art does not enable the production of mature terminally differentiated hepatocytes, likely due to the limitations of working in vitro and our lack of understanding of hepatocyte development (fetal to adult). Dr. Schwartz and team have used several approaches to identify the determinants of hepatocyte terminal differentiation: 1) Small Molecule Screen 2) Cellular organization during differentiation 3) Role of the microenvironment 4) Development of Cellular reporters of differentiation
