Development of an iPSC-derived human hepatocyte platform for drug development.

DESCRIPTION provided by applicant Human inducible pluripotent stem cells iPSCs proliferate readily and can be terminally differentiated into hepatocytes which potentially makes them an attractive cost effective resource compared to primary human hepatocytes Moreover the ability to standardize a platform to a single human donor or donor s who may include known genetic drug metabolism polymorphism s can eliminate or greatly reduce donor donor variability associated with primary hepatocytes Unfortunately it has been clearly demonstrated that differentiated iPSC derived hepatocytes iHCs though similar to primary hepatocytes in many ways retain certain andquot fetalandquot like aspects This includes increased expression of fetal like proteins e g fetal protein and decreased activity of specific cytochrome p enzymes e g the CYP A family which is responsible for metabolizing over of drugs Thus the pharmaceutical industry and regulatory agencies view the use of iHCs as promising but currently limited Attempts to andquot matureandquot these cells in novel hepatocyte platforms have not proven successful HemoShear is a biotechnology research company that utilizes patented methodologies to restore in vivo responsiveness to human primary cells in vitro We commercialized a human primary hepatocyte platform that combines physiological principles of controlled hemodynamics and transport to restore and maintain mature in vivo like differentiated phenotype morphology and metabolic function Hepatocytes in this platform respond to drugs and hormones at in vivo concentrations The purpose of this Fast Track SBIR is to develop an iHC platform using the HemoShear technology to mature iHC differentiated function and drug responses at physiological levels providing the framework for commercializing a much needed platform for drug safety and efficacy assessment PUBLIC HEALTH RELEVANCE Human inducible pluripotent stem cells iPSCs proliferate readily and can be terminally differentiated into hepatocytes which potentially makes them an attractive cost effective resource compared to primary human hepatocytes for drug discovery and development Unfortunately it has been clearly demonstrated that differentiated iPSC derived hepatocytes iHCs though similar to primary hepatocytes in many ways retain certain andquot fetalandquot like aspects Thus the pharmaceutical industry and regulatory agencies view the use of iHCs as promising but currently limited HemoShear is a biotechnology research company that utilizes patented methodologies to restore in vivo responsiveness to human primary cells in vitro The purpose of this Fast Track SBIR is to develop an iHC platform using the HemoShear technology to mature iHC differentiated function and drug responses at physiological levels providing the framework for commercializing a much needed platform for drug safety and efficacy assessment