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Transplantation of enteric nervous system stem cells rescues nitric oxide synthase deficient mouse colon

Author

Listed:
  • Conor J. McCann

    (Stem Cells and Regenerative Medicine, UCL Great Ormond Street Institute of Child Health)

  • Julie E. Cooper

    (Stem Cells and Regenerative Medicine, UCL Great Ormond Street Institute of Child Health)

  • Dipa Natarajan

    (Stem Cells and Regenerative Medicine, UCL Great Ormond Street Institute of Child Health)

  • Benjamin Jevans

    (Stem Cells and Regenerative Medicine, UCL Great Ormond Street Institute of Child Health)

  • Laura E. Burnett

    (Stem Cells and Regenerative Medicine, UCL Great Ormond Street Institute of Child Health)

  • Alan J. Burns

    (Stem Cells and Regenerative Medicine, UCL Great Ormond Street Institute of Child Health
    Erasmus Medical Center)

  • Nikhil Thapar

    (Stem Cells and Regenerative Medicine, UCL Great Ormond Street Institute of Child Health)

Abstract

Enteric nervous system neuropathy causes a wide range of severe gut motility disorders. Cell replacement of lost neurons using enteric neural stem cells (ENSC) is a possible therapy for these life-limiting disorders. Here we show rescue of gut motility after ENSC transplantation in a mouse model of human enteric neuropathy, the neuronal nitric oxide synthase (nNOS−/−) deficient mouse model, which displays slow transit in the colon. We further show that transplantation of ENSC into the colon rescues impaired colonic motility with formation of extensive networks of transplanted cells, including the development of nNOS+ neurons and subsequent restoration of nitrergic responses. Moreover, post-transplantation non-cell-autonomous mechanisms restore the numbers of interstitial cells of Cajal that are reduced in the nNOS−/− colon. These results provide the first direct evidence that ENSC transplantation can modulate the enteric neuromuscular syncytium to restore function, at the organ level, in a dysmotile gastrointestinal disease model.

Suggested Citation

  • Conor J. McCann & Julie E. Cooper & Dipa Natarajan & Benjamin Jevans & Laura E. Burnett & Alan J. Burns & Nikhil Thapar, 2017. "Transplantation of enteric nervous system stem cells rescues nitric oxide synthase deficient mouse colon," Nature Communications, Nature, vol. 8(1), pages 1-11, August.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15937
    DOI: 10.1038/ncomms15937
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    Cited by:

    1. Weikang Pan & Ahmed A. Rahman & Takahiro Ohkura & Rhian Stavely & Kensuke Ohishi & Christopher Y. Han & Abigail Leavitt & Aki Kashiwagi & Alan J. Burns & Allan M. Goldstein & Ryo Hotta, 2024. "Autologous cell transplantation for treatment of colorectal aganglionosis in mice," Nature Communications, Nature, vol. 15(1), pages 1-10, December.

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