Human Myelin Spheres for in Vitro Oligodendrocyte Maturation, Myelination and Neurological Disease Modeling

作者：Karan Ahuja, Roya Ramezankhani, Xinyu Wang, Thibaut Burg, Giulia Amos, Katrien Neyrinck, Alessio Silva, Geethika Arekatla, Eleanor Eva Cassidy, Fatemeharefeh Nami, Joke Terryn, Keimpe Wierda, Katlijn Vints, Niels Vandamme, Suresh Poovathingal, Ivo Lambrichts, Johannes V. Swinnen, Ludo Van Den Bosch, Lies De Groef, Lieve Moons, Catherine Verfaillie, Johan Neyts, Dirk Jochmans, Yoke Chin Chai · 发表于：Stem Cell Reviews and Reports · 年份：2026 · DOI：10.1007/s12015-026-11061-4 · 被引用次数：1 · 研究领域：Neurogenesis and neuroplasticity mechanisms、Nerve injury and regeneration、Neuroinflammation and Neurodegeneration Mechanisms

Demyelinating diseases, such as multiple sclerosis, damage the protective myelin sheaths of the central nervous system. The development of effective therapies has been hampered by the lack of models that accurately replicate human myelin biology. Here we present a novel method to generate human myelin spheres (MyS) by coculturing of hPSC-derived neuronal and oligodendrocyte precursor cells, to create myelinated neurons. Using multimodal analyses including confocal and (electron)microscopy, single-nuclei transcriptomics, lipidomics, and electrophysiology, we demonstrate myelination in MyS as early as six weeks into coculture. These myelinated structures mature over time into multilamellar and compacted myelin sheaths with lipid compositions and transcriptomic profiles mirror the temporal dynamics of in vivo human oligodendrocyte development and neuronal myelination, resembling those of late fetal oligodendrocytes. By employing lysolecithin-induced demyelination and Rabies virus infection experiments, we demonstrate the potential of MyS as an innovative, physiologically relevant platform for studying myelin-related neurodegeneration and neuroinfection.