Reporter gene-engineering of human induced pluripotent stem cells during differentiation renders in vivo traceable hepatocyte-like cells accessible

Abstract

Primary hepatocyte transplantation (HTx) is a safe cell therapy for patients with liver disease, but wider application is circumvented by poor cell engraftment due to limitations in hepatocyte quality and transplantation strategies. Hepatocyte-like cells (HLCs) derived from human induced pluripotent stem cells (hiPSC) are considered a promising alternative but also require optimisation of transplantation and are often transplanted prior to full maturation. Whole-body in vivo imaging would be highly beneficial to assess engraftment non-invasively and monitor the transplanted cells in the short and long-term.Here we report a lentiviral transduction approach designed to engineer hiPSC-derived HLCs during differentiation. This strategy resulted in the successful production of sodium iodide symporter (NIS)-expressing HLCs that were functionally characterised, transplanted into mice, and subsequently imaged using radionuclide tomography. Keywords: Cell tracking, Hepatocyte-like cells, Human sodium iodide symporter, Induced pluripotent stem cells, Lentivirus, Radionuclide imaging