Human Myelin Spheres for in Vitro Oligodendrocyte Maturation, Myelination and Neurological Disease Modeling
Year: 2026
Type: article
Abstract: 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.
Source: Stem Cell Reviews and Reports
Authors: 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
Language: English
Subfield: Developmental Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,390
Awards: G3869905229, Unravelling neuron-glia interactions in Wolfram syndrome through optic nerve-on-chip and in vivo base editing., Investigating fatty acid toxicity in amyotrophic lateral sclerosis, G5636686204, An all human iPSC derived model to study the role of microglia in neurodegeneration, OrganID: Organ-derived complex 2D/3D cultures in human disease
OpenAlex ID: W7125823344