Autologous cell transplantation for treatment of colorectal aganglionosis in mice

Weikang Pan, Ahmed A. Rahman, Takahiro Ohkura, Rhian Stavely, Kensuke Ohishi, Christopher Y. Han, Abigail Leavitt, Aki Kashiwagi, Alan J. Burns, Allan M. Goldstein and Ryo Hotta ()
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Weikang Pan: Massachusetts General Hospital, Harvard Medical School
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
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
Allan M. Goldstein: Massachusetts General Hospital, Harvard Medical School
Ryo Hotta: Massachusetts General Hospital, Harvard Medical School

Nature Communications, 2024, vol. 15, issue 1, 1-10

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-46793-9

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