Engineering human myelin microphysiological systems for testing patient treatment response in multiple sclerosis

Multiple sclerosis (MS) is an autoimmune disease targeting the central nervous system, marked by inflammation, loss of the protective myelin sheath, and progressive nerve damage. Regrettably, there is no definitive cure for MS, and personalized disease-modifying therapies are limited, at least in part due to the scarcity of accurate preclinical models that can faithfully replicate disease progression and assess individual patient responses to treatments.

In this study, researchers unveil a novel human myelin microphysiological system (myelin MPS) platform designed to bridge this gap. The platform successfully captures the disease phenotype and treatment response crucial for testing patient treatment responses. By cultivating neural organoids on 3D-printed devices with microfibers guiding their growth, and subsequently co-culturing these with oligodendrocyte progenitor cells, the research team could generate 96 distinct myelin MPS models within a standard well plate.

Utilizing this innovative myelin MPS platform, the researchers extracted autologous T cells and monocytes from both MS patients and healthy donors. This coculture with healthy myelinating neural tissues led to a notable increase in demyelination when induced by autologous cells from MS patients, compared to those from healthy individuals. Moreover, the study observed expansion of proinflammatory T-cell subsets and heightened myelin uptake by monocytes/macrophages, a hallmark of inflammatory responses in MS.

By incorporating advanced imaging techniques alongside flow cytometry, the researchers were able to differentiate between various patient profiles following treatment with common MS therapies: prednisone, glatiramer acetate, interferon {beta}-1a, and dimethyl fumarate. The myelin MPS platform offers a scalable, human-relevant approach for functional phenotyping and personalized evaluation of treatment response in MS patients.