Human-relevant preclinical in vitro models for studying hepatobiliary development and liver diseases using induced pluripotent stem cells

摘要

Pharmaceutical drug development and clinical testing is associated with billions of dollars, and often the time and money spent does not result in a viable drug formulation. The pharmaceutical industry has long relied on animal models for testing efficacy, toxicity and specificity of novel drugs. However, the studies cannot be fully relied upon, as animal models are not reflective of human pathophysiology and drug response, which results in drugs being pulled from development as late as at stage IV, after billions of dollars have already been invested in such an effort. With the advent of adult-induced pluripotent stem cell technology, came an era which offered the potential of pursing human relevant developmental and pathogenesis research and drug testing on patient-induced pluripotent stem cell-derived differentiated cells, consciously reflecting human responses with regard to drug safety, toxicity, efficacy, and side effects. Specifically, human-induced pluripotent stem cell-derived hepatobiliary cells and tissues may be a more human-relevant model system to address the biggest barrier to drug safety and approval: hepatotoxicity. In this review, we address the potential of human-induced pluripotent stem cell-based hepatobiliary differentiation technology as a means to study human liver development and hepatic cell fate determination, and to model liver diseases in an effort to develop a new human-relevant preclinical platform for drug development.