PDF(Pubmed)
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.
摘要：
神经肠疾病引起显著的发病率并且缺乏有效的治疗。本研究旨在测试在结肠神经节病模型中移植自体肠神经干细胞（ENSC）以挽救肠神经系统（ENS）的可行性。ENSC从Wnt1::Cre;R26iDTR小鼠的一段小肠中分离,其中通过注射白喉毒素同时产生局灶性结肠神经节病。分离自体ENSC，展开,用慢病毒-GFP标记，并在体内移植到神经节段。ENSC分化为神经元和神经胶质，集群形成新神经节，如电场刺激和光遗传学所示，并恢复结肠收缩活动。使用结肠神经节病的非致死模型，我们的结果证明了自体ENSC治疗改善神经肠疾病功能结局的潜力，为这种基于再生细胞的方法的临床应用奠定了基础。
