2025年6月24日出版的《细胞—干细胞》杂志发表了美国科学家的一项最新研究成果。来自美国雪松西奈理事会再生医学研究所的Clive N. Svendsen小组研究出利用ipsc衍生的脊髓运动神经元和一体化血脑样屏障建立散发性ALS器官芯片模型。

该课题组人员将来自早发性疾病患者的MNs与脑微血管内皮样细胞结合在该课题组人员称为脊髓芯片（SC-chips）的微流体装置中，并添加培养基流，从而促进神经元成熟并改善细胞健康。SC芯片的大量转录组学和蛋白质组学分析揭示了对照组和ALS样本之间的差异，包括神经丝水平的增加。单核RNA测序显示存在两个MN亚群和als特异性谷氨酸能和突触信号的失调。这种ALS SC芯片模型产生了多种成熟的MNs，以更好地了解ALS病理，该模型具有活跃的血脑屏障样系统，可用于未来的药物筛选。

据介绍，肌萎缩性侧索硬化症（ALS）是一种致命的神经退行性疾病，其中大脑和脊髓的运动神经元（MNs）退化，导致瘫痪。从患者特异性诱导多能干细胞（iPSCs）产生MNs可能有助于阐明疾病的早期阶段。

附：英文原文

Title: An organ-chip model of sporadic ALS using iPSC-derived spinal cord motor neurons and an integrated blood-brain-like barrier

Author: Deepti Lall, Michael J. Workman, Samuel Sances, Briana N. Ondatje, Shaughn Bell, George Lawless, Amanda Woodbury, Dylan West, Amanda Meyer, Andrea Matlock, Vineet Vaibhav, Jennifer E. Van Eyk, Clive N. Svendsen

Issue&Volume: 2025-06-24

Abstract: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder in which motor neurons (MNs) of the brain and spinal cord degenerate, leading to paralysis. Generating MNs from patient-specific induced pluripotent stem cells (iPSCs) may help elucidate early stages of disease. Here, we combined MNs from patients with early-onset disease with brain microvascular endothelial-like cells in a microfluidic device we termed spinal cord chips (SC-chips) and added media flow, which enhanced neuronal maturation and improved cellular health. Bulk transcriptomic and proteomic analyses of SC-chips revealed differences between control and ALS samples, including increased levels of neurofilaments. Single-nuclei RNA sequencing revealed the presence of two MN subpopulations and an ALS-specific dysregulation of glutamatergic and synaptic signaling. This ALS SC-chip model generates a diversity of mature MNs to better understand ALS pathology in a model that has an active blood-brain barrier-like system for future drug screening.

DOI: 10.1016/j.stem.2025.05.015

Source: https://www.cell.com/cell-stem-cell/abstract/S1934-5909(25)00222-X