Intestinal Epithelial Stem Cell Transplants As a Novel Therapy for Cerebrovascular Stroke

Overview

Journal Brain Behav Immun

Publisher Elsevier

Specialties Allergy & Immunology
Neurology
Psychiatry

Date 2022 Nov 3

PMID 36328163

Authors

Kathiresh Kumar Mani

Yumna El-Hakim

Taylor E Branyan

Nadia Samiya

Sivani Pandey

Maria T Grimaldo

Ali Habbal

Anna Wertz

Farida Sohrabji

Affiliations

Soon will be listed here.

Abstract

Almost 2/3 of stroke survivors exhibit vascular cognitive impairment and a third of stroke patients will develop dementia 1-3 years after stroke. These dire consequences underscore the need for effective stroke therapies. In addition to its damaging effects on the brain, stroke rapidly dysregulates the intestinal epithelium, resulting in elevated blood levels of inflammatory cytokines and toxic gut metabolites due to a 'leaky' gut. We tested whether repairing the gut via intestinal epithelial stem cell (IESC) transplants would also improve stroke recovery. Organoids containing IESCs derived from young rats transplanted into older rats after stroke were incorporated into the gut, restored stroke-induced gut dysmorphology and decreased gut permeability, and reduced circulating levels of endotoxin LPS and the inflammatory cytokine IL-17A. Remarkably, IESC transplants also improved stroke-induced acute (4d) sensory-motor disability and chronic (30d) cognitive-affective function. Moreover, IESCs from older animals displayed senescent features and were not therapeutic for stroke. These data underscore the gut as a critical therapeutic target for stroke and demonstrate the effectiveness of gut stem cell therapy.

Citing Articles

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Current applications of intestinal organoids: a review.

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