This report describes a human myelin MPS (myelin microphysiological system) developed to model key features of multiple sclerosis (MS) and to test individualized treatment responses. The platform aims to address the shortage of preclinical human models that can faithfully recapitulate MS pathology and enable functional phenotyping at the individual-patient level.
The platform is built by culturing neural organoids on 3D-printed devices that incorporate directional microfibers. After establishing the neural organoids on these scaffolds, the cultures are cocultured with oligodendrocyte progenitor cells to promote myelination of axonal structures within the engineered tissues.
Using the described fabrication and culture workflow, the investigators generated arrays of myelinated constructs compatible with conventional well-plate formats. The method yields up to 96 myelin MPS models per well plate, providing a scalable format for comparative experiments and higher-throughput testing of cell interactions and therapeutics.
To evaluate immune-mediated pathology, the platform was cocultured with autologous immune cells derived from study participants. Specifically, T cells and monocytes isolated from MS patients were introduced to the healthy, myelinating neural tissues in the myelin MPS. When compared with immune cells from healthy donors, autologous MS-derived immune cells induced substantially greater demyelination in the engineered tissues.
Coculture of the myelin MPS with patient immune cells produced several measurable cellular responses. The investigators observed expansion of proinflammatory T-cell subsets during coculture with MS-derived immune cells. In parallel, monocytes and macrophages demonstrated increased uptake of myelin material. These readouts—greater demyelination, proinflammatory T-cell expansion, and increased myelin phagocytosis—together reflect immune-driven myelin injury captured by the platform.
The platform integrates imaging-based measures and flow-cytometric features to generate multidimensional phenotypes. These combined readouts were used to distinguish between samples from healthy donors and MS patients, and to further separate untreated-MS profiles from those classified as responders or nonresponders after treatment exposure. The work emphasizes the use of orthogonal assay modalities to improve discrimination of pathophysiologic and therapeutic effects.
The authors applied several clinically used MS treatments to the myelin MPS to evaluate differential responses. Specifically, the platform was used to test prednisone, glatiramer acetate, interferon β-1a, and dimethyl fumarate. Integration of the imaging and flow-cytometric features after drug exposure enabled classification of profiles into healthy-donor, untreated-MS, responder, and nonresponder groups. The source abstract reports that these distinctions were achievable on the platform; specific quantitative outcomes, sample sizes, and detailed response criteria were not reported in the abstract.
The myelin MPS platform offers a human-pathophysiology–relevant system for functional phenotyping and individualized evaluation of treatment response in MS. Because the system is compatible with autologous immune cell coculture and is scalable to 96 units per plate, it could be used to compare patient-specific immune effects on myelinated tissue and to test multiple therapeutic agents or dosing conditions in parallel. The authors present the system as a tool to help bridge gaps between patient heterogeneity and selection of effective disease-modifying therapies.
The available source material is an abstract and highlights key findings and platform capabilities but does not report several experimental details. The following were not reported in the abstract and therefore cannot be asserted here: the number of patient and control donors tested, specific quantitative metrics for demyelination or immune activation, statistical analyses, time courses, viability or long-term stability of the myelinated constructs, and protocol step-by-step parameters. Users should consult the full preprint for complete methods, data, and validation metrics.
The study is presented as a preprint posted September 18, 2026, on bioRxiv (doi: https://doi.org/10.64898/2026.09.12.750449). The authors declared no competing interests in the source document.
This summary preserves the scope and main findings presented in the source abstract and refrains from adding details that were not reported there.