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

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...

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Main Authors: Candice Ashmore-Harris, Samuel JI Blackford, Benjamin Grimsdell, Ewelina Kurtys, Marlies C Glatz, Tamir S Rashid, Gilbert O Fruhwirth
Format: Article
Language:English
Published: Elsevier 2019-12-01
Series:Stem Cell Research
Online Access:http://www.sciencedirect.com/science/article/pii/S1873506119302296
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spelling doaj-18160a1e0fba4e229b85aa66180b66fa2020-11-25T02:13:56ZengElsevierStem Cell Research1873-50612019-12-0141Reporter gene-engineering of human induced pluripotent stem cells during differentiation renders in vivo traceable hepatocyte-like cells accessibleCandice Ashmore-Harris0Samuel JI Blackford1Benjamin Grimsdell2Ewelina Kurtys3Marlies C Glatz4Tamir S Rashid5Gilbert O Fruhwirth6Imaging Therapy and Cancer Group, Department of Imaging Chemistry and Biology, School of Biomedical Engineering and Imaging Sciences, St Thomas’ Hospital, King's College London (KCL), London, SE1 7EH, UK; Centre for Stem Cells and Regenerative Medicine, School of Basic and Medical Biosciences, Guy's Hospital, KCL, London SE1 9RT, UKCentre for Stem Cells and Regenerative Medicine, School of Basic and Medical Biosciences, Guy's Hospital, KCL, London SE1 9RT, UKImaging Therapy and Cancer Group, Department of Imaging Chemistry and Biology, School of Biomedical Engineering and Imaging Sciences, St Thomas’ Hospital, King's College London (KCL), London, SE1 7EH, UK; Centre for Human and Applied Physiological Sciences, School of Basic and Medical Biosciences, Shepherd's House, King's College London, SE1 1UL, UKImaging Therapy and Cancer Group, Department of Imaging Chemistry and Biology, School of Biomedical Engineering and Imaging Sciences, St Thomas’ Hospital, King's College London (KCL), London, SE1 7EH, UKImaging Therapy and Cancer Group, Department of Imaging Chemistry and Biology, School of Biomedical Engineering and Imaging Sciences, St Thomas’ Hospital, King's College London (KCL), London, SE1 7EH, UKCentre for Stem Cells and Regenerative Medicine, School of Basic and Medical Biosciences, Guy's Hospital, KCL, London SE1 9RT, UK; Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London SE5 9RS, UKImaging Therapy and Cancer Group, Department of Imaging Chemistry and Biology, School of Biomedical Engineering and Imaging Sciences, St Thomas’ Hospital, King's College London (KCL), London, SE1 7EH, UK; Corresponding author.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 imaginghttp://www.sciencedirect.com/science/article/pii/S1873506119302296
collection DOAJ
language English
format Article
sources DOAJ
author Candice Ashmore-Harris
Samuel JI Blackford
Benjamin Grimsdell
Ewelina Kurtys
Marlies C Glatz
Tamir S Rashid
Gilbert O Fruhwirth
spellingShingle Candice Ashmore-Harris
Samuel JI Blackford
Benjamin Grimsdell
Ewelina Kurtys
Marlies C Glatz
Tamir S Rashid
Gilbert O Fruhwirth
Reporter gene-engineering of human induced pluripotent stem cells during differentiation renders in vivo traceable hepatocyte-like cells accessible
Stem Cell Research
author_facet Candice Ashmore-Harris
Samuel JI Blackford
Benjamin Grimsdell
Ewelina Kurtys
Marlies C Glatz
Tamir S Rashid
Gilbert O Fruhwirth
author_sort Candice Ashmore-Harris
title Reporter gene-engineering of human induced pluripotent stem cells during differentiation renders in vivo traceable hepatocyte-like cells accessible
title_short Reporter gene-engineering of human induced pluripotent stem cells during differentiation renders in vivo traceable hepatocyte-like cells accessible
title_full Reporter gene-engineering of human induced pluripotent stem cells during differentiation renders in vivo traceable hepatocyte-like cells accessible
title_fullStr Reporter gene-engineering of human induced pluripotent stem cells during differentiation renders in vivo traceable hepatocyte-like cells accessible
title_full_unstemmed Reporter gene-engineering of human induced pluripotent stem cells during differentiation renders in vivo traceable hepatocyte-like cells accessible
title_sort reporter gene-engineering of human induced pluripotent stem cells during differentiation renders in vivo traceable hepatocyte-like cells accessible
publisher Elsevier
series Stem Cell Research
issn 1873-5061
publishDate 2019-12-01
description 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
url http://www.sciencedirect.com/science/article/pii/S1873506119302296
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