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

Stem Cell Res. 2019 Dec;41:101599. doi: 10.1016/j.scr.2019.101599. Epub 2019 Oct 15.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation*
  • Genes, Reporter*
  • Genetic Engineering
  • Genetic Vectors*
  • Hepatocytes / metabolism*
  • Humans
  • Induced Pluripotent Stem Cells / metabolism*
  • Lentivirus*
  • Transduction, Genetic*