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Autologous cell transplantation for treatment of colorectal aganglionosis in mice

Author

Listed:
  • Weikang Pan

    (Massachusetts General Hospital, Harvard Medical School
    The second affiliated hospital of Xi’an Jiaotong University)

  • Ahmed A. Rahman

    (Massachusetts General Hospital, Harvard Medical School)

  • Takahiro Ohkura

    (Massachusetts General Hospital, Harvard Medical School)

  • Rhian Stavely

    (Massachusetts General Hospital, Harvard Medical School)

  • Kensuke Ohishi

    (Massachusetts General Hospital, Harvard Medical School
    Wakunaga Pharmaceutical Co., Ltd.)

  • Christopher Y. Han

    (Massachusetts General Hospital, Harvard Medical School)

  • Abigail Leavitt

    (Massachusetts General Hospital, Harvard Medical School)

  • Aki Kashiwagi

    (Massachusetts General Hospital, Harvard Medical School)

  • Alan J. Burns

    (Massachusetts General Hospital, Harvard Medical School
    UCL Great Ormond Street Institute of Child Health)

  • Allan M. Goldstein

    (Massachusetts General Hospital, Harvard Medical School)

  • Ryo Hotta

    (Massachusetts General Hospital, Harvard Medical School)

Abstract

Neurointestinal diseases cause significant morbidity and effective treatments are lacking. This study aimes to test the feasibility of transplanting autologous enteric neural stem cells (ENSCs) to rescue the enteric nervous system (ENS) in a model of colonic aganglionosis. ENSCs are isolated from a segment of small intestine from Wnt1::Cre;R26iDTR mice in which focal colonic aganglionosis is simultaneously created by diphtheria toxin injection. Autologous ENSCs are isolated, expanded, labeled with lentiviral-GFP, and transplanted into the aganglionic segment in vivo. ENSCs differentiate into neurons and glia, cluster to form neo-ganglia, and restore colonic contractile activity as shown by electrical field stimulation and optogenetics. Using a non-lethal model of colonic aganglionosis, our results demonstrate the potential of autologous ENSC therapy to improve functional outcomes in neurointestinal disease, laying the groundwork for clinical application of this regenerative cell-based approach.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46793-9
    DOI: 10.1038/s41467-024-46793-9
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    References listed on IDEAS

    as
    1. Faranak Fattahi & Julius A Steinbeck & Sonja Kriks & Jason Tchieu & Bastian Zimmer & Sarah Kishinevsky & Nadja Zeltner & Yvonne Mica & Wael El-Nachef & Huiyong Zhao & Elisa de Stanchina & Michael D. G, 2016. "Deriving human ENS lineages for cell therapy and drug discovery in Hirschsprung disease," Nature, Nature, vol. 531(7592), pages 105-109, March.
    2. 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.
    Full references (including those not matched with items on IDEAS)

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