近日，美国加州大学教授Faranak Fattahi及其课题组发现了来源于人造血干细胞的氮能神经元移植可改善小鼠肠道运动障碍。相关论文发表在2025年6月25日出版的《自然》杂志上。

在这里，研究小组介绍了一个基于人类多能干细胞（hPSCs）的平台，用于治疗胃肠道运动障碍。通过无偏筛选，该团队确定了可调节NO神经元活性并增强无主题结肠组织体外运动性的候选药物。该课题组研究人员建立了一个高通量策略来定义驱动NO神经元规范的发育程序，并发现抑制血小板衍生生长因子受体（PDGFRs）可促进其从肠神经系统前体分化。将这些神经元移植到No-神经元缺陷小鼠体内，可使其自动植入并改善胃肠道运动，为神经退行性胃肠道疾病提供了一种有希望的细胞治疗方法。这些研究为理解和治疗肠道神经病变提供了一个新的框架。

据悉，胃肠（GI）运动障碍是一个主要的医学挑战，很少有有效的治疗方法。这些疾病通常是由肠道神经系统中产生抑制一氧化氮（NO）的运动神经元功能障碍引起的，而这些神经元对调节肠道运动至关重要。NO神经元的丧失或功能障碍与严重的疾病有关，包括失弛缓症、胃轻瘫、假性肠梗阻和慢性便秘。

附：英文原文

Title: Engrafted nitrergic neurons derived from hPSCs improve gut dysmotility in mice

Author: Majd, Homa, Samuel, Ryan M., Cesiulis, Andrius, Ramirez, Jonathan T., Kalantari, Ali, Barber, Kevin, Farahvashi, Sina, Ghazizadeh, Zaniar, Majd, Alireza, Chemel, Angeline K., Richter, Mikayla N., Das, Subhamoy, Bendrick, Jacqueline L., Keefe, Matthew G., Wang, Jeffrey, Shiv, Rahul K., Bhat, Samyukta, Khoroshkin, Matvei, Yu, Johnny, Nowakowski, Tomasz J., Wen, Kwun Wah, Goodarzi, Hani, Thapar, Nikhil, Kaltschmidt, Julia A., McCann, Conor J., Fattahi, Faranak

Issue&Volume: 2025-06-25

Abstract: Gastrointestinal (GI) motility disorders represent a major medical challenge, with few effective therapies available. These disorders often result from dysfunction of inhibitory nitric oxide (NO)-producing motor neurons in the enteric nervous system, which are essential for regulating gut motility. Loss or dysfunction of NO neurons is linked to severe conditions, including achalasia, gastroparesis, intestinal pseudo-obstruction and chronic constipation1,2. Here we introduce a platform based on human pluripotent stem cells (hPSCs) for therapeutic development targeting GI motility disorders. Using an unbiased screen, we identified drug candidates that modulate NO neuron activity and enhance motility in mouse colonic tissue ex vivo. We established a high-throughput strategy to define developmental programs driving the specification of NO neurons and found that inhibition of platelet-derived growth factor receptors (PDGFRs) promotes their differentiation from precursors of the enteric nervous system. Transplantation of these neurons into NO-neuron-deficient mice led to robust engraftment and improved GI motility, offering a promising cell-based therapy for neurodegenerative GI disorders. These studies provide a new framework for understanding and treating enteric neuropathies.

DOI: 10.1038/s41586-025-09208-3

Source: https://www.nature.com/articles/s41586-025-09208-3