Autologous Cell Transplantation for Treatment of Colorectal Aganglionosis in Mice

Overview

Journal Nat Commun

Specialty Biology

Date 2024 Mar 21

PMID 38509106

Authors

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

Affiliations

Soon will be listed here.

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.

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