冲程(发动机)
医学
干细胞
干细胞疗法
内科学
移植
病理
生物
细胞生物学
机械工程
工程类
作者
Kathiresh Kumar Mani,Yumna El-Hakim,Taylor Branyan,Nadia Samiya,Sivani Pandey,Maria T. Grimaldo,Ali Habbal,Anna Wertz,Farida Sohrabji
标识
DOI:10.1016/j.bbi.2022.10.015
摘要
Almost 2/3rds 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.
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