英国伦敦大学学院Emad Moeendarbary小组开发出用于髓鞘形成研究的可调水凝胶微柱阵列。这一研究成果于2026年3月30日发表在国际顶尖学术期刊《自然—方法学》上。

为了模拟调节髓鞘形成的关键生物力学线索，课题组研究人员开发了一种可调的基于水凝胶的微柱阵列系统，该系统模拟了轴突的三维结构和柔软度。该平台支持少突胶质细胞的长期培养和啮齿动物和人类少突胶质细胞多层致密髓磷脂的形成。通过共聚焦和透射电镜，研究人员观察到免疫染色的髓鞘厚度与髓鞘包裹数之间存在很强的线性相关性，从而实现髓鞘形成的高含量定量。

在病理生理范围内的柱刚度、直径和表面化学的系统变化表明，轴突样底物的力学和几何特性对少突胶质细胞分化和髓鞘包裹具有关键的调节作用。重要的是，该课题组证明药理学药物对髓鞘形成表现出刚度依赖效应，这表明过度刚性的体外模型可能产生假阳性的药物命中。该平台为解剖少突胶质细胞生物学和发现多发性硬化症等疾病的髓鞘再生疗法提供了生理学相关的高通量检测。

据介绍，少突胶质细胞通过髓鞘轴突实现中枢神经系统的快速信号传递。

附：英文原文

Title: Tunable hydrogel-based micropillar arrays for myelination studies

Author: Lasli, Soufian, Vinel, Claire, Agrawal, Ayushi, Javanmardi, Yousef, Pedarzani, Paola, Garcia Diaz, Beatriz, Garcia-Leon, Juan Antonio, Djordjevic, Boris, White, Ian J., Sheridan, Graham K., Richardson, William D., Moeendarbary, Emad

Issue&Volume: 2026-03-30

Abstract: Oligodendrocytes enable rapid central nervous system signaling by myelinating axons. Here, to model key biomechanical cues regulating myelination, we developed a tunable hydrogel-based micropillar array system that mimics the three-dimensional architecture and softness of axons. This platform supports the long-term culture of oligodendrocytes and robust formation of multilayered compact myelin by rodent and human oligodendrocytes. Using confocal and transmission electron microscopy, we observed a strong linear correlation between immunostained myelin thickness and the number of myelin wraps, enabling high-content quantification of myelination. Systematic variation of pillar stiffness, diameter and surface chemistry within pathophysiological ranges revealed that both mechanical and geometric properties of axon-like substrates critically regulate oligodendrocyte differentiation and myelin wrapping. Importantly, we demonstrate that pharmacological agents exhibit stiffness-dependent effects on myelination, suggesting that overly rigid in vitro models may yield false-positive drug hits. This platform offers a physiologically relevant, high-throughput assay for dissecting oligodendrocyte biology and discovering remyelinating therapies for diseases such as multiple sclerosis.

DOI: 10.1038/s41592-026-03048-3

Source: https://www.nature.com/articles/s41592-026-03048-3