High transduction efficiency of circulating first trimester fetal mesenchymal stem cells: potential targets for in utero ex vivo gene therapy

Authors

  • Cesare Campagnoli,

    1. Institute of Reproductive and Developmental Biology, Imperial College Faculty of Medicine, Hammersmith Campus, London, UK
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    • 1

      These authors contributed equally to this work.

  • Ilaria Bellantuono,

    1. Department of Immunology, Imperial College Faculty of Medicine, Hammersmith Campus, London, UK
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    • 1

      These authors contributed equally to this work.

    • 2

      Stem Cell Research Laboratory, Giving for Living Research Centre, Royal Manchester Children Hospital, Manchester, UK.

  • Sailesh Kumar,

    1. Institute of Reproductive and Developmental Biology, Imperial College Faculty of Medicine, Hammersmith Campus, London, UK
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  • Leslie J. Fairbairn,

    1. Department of Gene Therapy, Paterson Institute for Cancer Research, Manchester, UK
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  • Irene Roberts,

    1. Department of Haematology, Imperial College Faculty of Medicine, Hammersmith Campus, London, UK
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  • Nicholas M. Fisk

    Corresponding author
    1. Institute of Reproductive and Developmental Biology, Imperial College Faculty of Medicine, Hammersmith Campus, London, UK
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*Professor N. M. Fisk, Institute of Reproductive and Developmental Biology, Imperial College, Hammersmith Campus, Du Cane Road, London W12 ONN, UK.

Abstract

We recently reported the existence of fetal mesenchymal stem cells in first trimester fetal blood. Here we demonstrate that fetal mesenchymal stem cells from as early as eight weeks of gestation can be retrovirally transduced with 99% efficiency without selection. Circulating fetal mesenchymal stem cells are known to readily expand and differentiate into multiple tissue types both in vitro and in vivo, and might be suitable vehicles for prenatal gene delivery. With advances in early fetal blood sampling techniques, we suggest that genetic disorders causing irreversible damage before birth could be treated in utero in the late first/early second trimester by genetically manipulated autologous fetal stem cells.

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