{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T12:03:42Z","timestamp":1790165022316,"version":"4.1.0"},"posted":{"date-parts":[[2026,9,18]]},"group-title":"Bioengineering","reference-count":65,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Multiple sclerosis (MS) is an autoimmune disease of the central nervous system characterized by neuroinflammation, demyelination, and neurodegeneration, associated with a complex interplay between the innate and adaptive immune systems. Currently, no cure is available for MS, and personalized disease-modifying treatment remains largely limited, partially due to the lack of preclinical human models that can faithfully recapitulate disease pathology and evaluate treatment responses at the individual-patient level. Here, we report a human myelin microphysiological system (myelin MPS) platform that recaptures disease phenotype and treatment response for testing patient treatment response. By culturing neural organoids on 3D-printed devices containing directional microfibers, followed by coculture with oligodendrocyte progenitor cells, 96 myelin MPS models can be generated within a conventional well plate. Using this myelin MPS platform, autologous T cells and monocytes from MS patients induced substantially greater demyelination than those from healthy donors, accompanied by expansion of proinflammatory T-cell subsets and increased myelin uptake by monocytes\/macrophages after coculture with these healthy myelinating neural tissues. Integration of imaging and flow-cytometric features distinguished healthy-donor, untreated-MS, responder, and nonresponder profiles following treatment with prednisone, glatiramer acetate, interferon \u03b2-1a, or dimethyl fumarate. Thus, the myelin MPS platform provides a scalable, human pathophysiology-relevant platform for functional phenotyping and individualized treatment-response evaluation in MS.<\/jats:p>","DOI":"10.64898\/2026.09.12.750449","type":"posted-content","created":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T00:35:11Z","timestamp":1789778111000},"source":"Crossref","is-referenced-by-count":0,"title":["Engineering human myelin microphysiological systems for testing patient treatment response in multiple sclerosis"],"prefix":"10.64898","author":[{"given":"Chunhui","family":"Tian","sequence":"first","affiliation":[{"name":"Department of Intelligent Systems Engineering, Indiana University, Bloomington, IN 47405, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Ao","sequence":"additional","affiliation":[{"name":"Department of Intelligent Systems Engineering, Indiana University, Bloomington, IN 47405, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongwei","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Intelligent Systems Engineering, Indiana University, Bloomington, IN 47405, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiansen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Intelligent Systems Engineering, Indiana University, Bloomington, IN 47405, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nian","family":"Wang","sequence":"additional","affiliation":[{"name":"Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Tchieu","sequence":"additional","affiliation":[{"name":"Center for Stem Cell and Organoid Medicine (CuSTOM), Division of Pulmonary Biology, Division of Developmental Biology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229, United States"},{"name":"University of Cincinnati School of Medicine, Cincinnati, OH 45229, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui-Chen","family":"Lu","sequence":"additional","affiliation":[{"name":"Gill Institute for Biomolecular Science, and Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN 47405, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken","family":"Mackie","sequence":"additional","affiliation":[{"name":"Gill Institute for Biomolecular Science, and Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN 47405, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingxia","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology and Perioperative Medicine, David Geffen School of Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Biology, University of California, Los Angeles, CA 90095"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Intelligent Systems Engineering, Indiana University, Bloomington, IN 47405, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026092304300681000_2026.09.12.750449v1.1","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1038\/nrneurol.2010.147","article-title":"Autoimmune associations in multiple sclerosis","volume":"6","year":"2010","journal-title":"Nature Reviews Neurology"},{"key":"2026092304300681000_2026.09.12.750449v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81107-1"},{"key":"2026092304300681000_2026.09.12.750449v1.3","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a029025"},{"key":"2026092304300681000_2026.09.12.750449v1.4","doi-asserted-by":"crossref","first-page":"286","DOI":"10.3389\/fphar.2019.00286","article-title":"Targeting microglia and macrophages: a potential treatment strategy for multiple sclerosis","volume":"10","year":"2019","journal-title":"Frontiers in pharmacology"},{"key":"2026092304300681000_2026.09.12.750449v1.5","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/12.12.1641"},{"key":"2026092304300681000_2026.09.12.750449v1.6","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.26858"},{"key":"2026092304300681000_2026.09.12.750449v1.7","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1017\/S0317167100013500","article-title":"MS patients report excellent compliance with oral prednisone for acute relapses","volume":"39","year":"2012","journal-title":"Canadian journal of neurological sciences"},{"key":"2026092304300681000_2026.09.12.750449v1.8","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1007\/s40265-016-0639-3","article-title":"Predictors of response to multiple sclerosis therapeutics in individual patients","volume":"76","year":"2016","journal-title":"Drugs"},{"key":"2026092304300681000_2026.09.12.750449v1.9","doi-asserted-by":"publisher","DOI":"10.1007\/s40263-013-0042-5"},{"key":"2026092304300681000_2026.09.12.750449v1.10","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1001\/jamaneurol.2018.4905","article-title":"Clinical outcomes of escalation vs early intensive disease-modifying therapy in patients with multiple sclerosis","volume":"76","year":"2019","journal-title":"JAMA neurology"},{"key":"2026092304300681000_2026.09.12.750449v1.11","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/S1474-4422(20)30067-3","article-title":"Timing of high-efficacy therapy for multiple sclerosis: a retrospective observational cohort study","volume":"19","year":"2020","journal-title":"The Lancet Neurology"},{"key":"2026092304300681000_2026.09.12.750449v1.12","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2018.20588"},{"key":"2026092304300681000_2026.09.12.750449v1.13","doi-asserted-by":"publisher","DOI":"10.1038\/nature12517"},{"key":"2026092304300681000_2026.09.12.750449v1.14","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/nmeth.3415","article-title":"Functional cortical neurons and astrocytes from human pluripotent stem cells in 3D culture","volume":"12","year":"2015","journal-title":"Nature methods"},{"key":"2026092304300681000_2026.09.12.750449v1.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2019.08.002"},{"key":"2026092304300681000_2026.09.12.750449v1.16","doi-asserted-by":"crossref","first-page":"1696937","DOI":"10.3389\/fnins.2025.1696937","article-title":"Established and emerging new approach methodologies in neuroscience","volume":"19","year":"2025","journal-title":"Frontiers in Neuroscience"},{"key":"2026092304300681000_2026.09.12.750449v1.17","doi-asserted-by":"publisher","DOI":"10.1038\/nature22047"},{"key":"2026092304300681000_2026.09.12.750449v1.18","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1654-9"},{"key":"2026092304300681000_2026.09.12.750449v1.19","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adu2708"},{"key":"2026092304300681000_2026.09.12.750449v1.20","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-021-00923-4"},{"key":"2026092304300681000_2026.09.12.750449v1.21","doi-asserted-by":"publisher","DOI":"10.1242\/bio.059845"},{"key":"2026092304300681000_2026.09.12.750449v1.22","doi-asserted-by":"crossref","unstructured":"Fagiani, F. et al. A glia-enriched stem cell 3D model of the human brain mimics the glialimmune neurodegenerative phenotypes of multiple sclerosis. Cell Reports Medicine 5 (2024).","DOI":"10.1101\/2024.06.20.597748"},{"key":"2026092304300681000_2026.09.12.750449v1.23","doi-asserted-by":"crossref","first-page":"eadp7047","DOI":"10.1126\/scitranslmed.adp7047","article-title":"Human myelinated brain organoids with integrated microglia as a model for myelin repair and remyelinating therapies","volume":"17","year":"2025","journal-title":"Science translational medicine"},{"key":"2026092304300681000_2026.09.12.750449v1.24","first-page":"1","article-title":"The physiology of foamy phagocytes in multiple sclerosis","volume":"6","year":"2018","journal-title":"Acta neuropathologica communications"},{"key":"2026092304300681000_2026.09.12.750449v1.25","first-page":"265","article-title":"The role of antigen presenting cells in multiple sclerosis","volume":"1812","year":"2011","journal-title":"Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease"},{"key":"2026092304300681000_2026.09.12.750449v1.26","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1038\/s41582-019-0253-6","article-title":"When encephalitogenic T cells collaborate with microglia in multiple sclerosis","volume":"15","year":"2019","journal-title":"Nature Reviews Neurology"},{"key":"2026092304300681000_2026.09.12.750449v1.27","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(200203)32:3<606::AID-IMMU606>3.0.CO;2-D"},{"key":"2026092304300681000_2026.09.12.750449v1.28","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2015.00539"},{"key":"2026092304300681000_2026.09.12.750449v1.29","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.27661"},{"key":"2026092304300681000_2026.09.12.750449v1.30","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0008668"},{"key":"2026092304300681000_2026.09.12.750449v1.31","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.21.12033"},{"key":"2026092304300681000_2026.09.12.750449v1.32","doi-asserted-by":"crossref","first-page":"5920","DOI":"10.4049\/jimmunol.168.11.5920","article-title":"The human T cell response to myelin oligodendrocyte glycoprotein: a multiple sclerosis family-based study","volume":"168","year":"2002","journal-title":"The Journal of Immunology"},{"key":"2026092304300681000_2026.09.12.750449v1.33","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00760"},{"key":"2026092304300681000_2026.09.12.750449v1.34","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-10-1"},{"key":"2026092304300681000_2026.09.12.750449v1.35","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-8-85"},{"key":"2026092304300681000_2026.09.12.750449v1.36","doi-asserted-by":"publisher","DOI":"10.1111\/ene.12883"},{"key":"2026092304300681000_2026.09.12.750449v1.37","first-page":"1","article-title":"Therapeutic efficacy of dimethyl fumarate in relapsing-remitting multiple sclerosis associates with ROS pathway in monocytes","volume":"10","year":"2019","journal-title":"Nature communications"},{"key":"2026092304300681000_2026.09.12.750449v1.38","first-page":"134","article-title":"The diagnosis of multiple sclerosis and the various related demyelinating syndromes: a critical review","volume":"48","year":"2014","journal-title":"Journal of autoimmunity"},{"key":"2026092304300681000_2026.09.12.750449v1.39","doi-asserted-by":"publisher","DOI":"10.1016\/j.clineuro.2004.02.004"},{"key":"2026092304300681000_2026.09.12.750449v1.40","doi-asserted-by":"publisher","DOI":"10.1007\/s11940-015-0354-5"},{"key":"2026092304300681000_2026.09.12.750449v1.41","doi-asserted-by":"publisher","DOI":"10.1097\/wco.0000000000000937"},{"key":"2026092304300681000_2026.09.12.750449v1.42","doi-asserted-by":"crossref","unstructured":"Sol, N. et al. Blood platelet RNA enables the detection of multiple sclerosis. Multiple Sclerosis Journal\u2013Experimental, Translational and Clinical 6, 2055217320946784 (2020).","DOI":"10.1177\/2055217320946784"},{"key":"2026092304300681000_2026.09.12.750449v1.43","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2015.07.014"},{"key":"2026092304300681000_2026.09.12.750449v1.44","first-page":"1","article-title":"A blood-based metabolomics test to distinguish relapsing\u2013remitting and secondary progressive multiple sclerosis: addressing practical considerations for clinical application","volume":"10","year":"2020","journal-title":"Scientific reports"},{"key":"2026092304300681000_2026.09.12.750449v1.45","doi-asserted-by":"crossref","unstructured":"Esaulova, E. et al. Single-cell RNA-seq analysis of human CSF microglia and myeloid cells in neuroinflammation. Neurology-Neuroimmunology Neuroinflammation 7 (2020).","DOI":"10.1212\/NXI.0000000000000732"},{"key":"2026092304300681000_2026.09.12.750449v1.46","first-page":"1","article-title":"Multi-parameter immune profiling of peripheral blood mononuclear cells by multiplexed single-cell mass cytometry in patients with early multiple sclerosis","volume":"9","year":"2019","journal-title":"Scientific reports"},{"key":"2026092304300681000_2026.09.12.750449v1.47","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.1999.00816.x"},{"key":"2026092304300681000_2026.09.12.750449v1.48","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1128\/cdli.3.4.411-416.1996","article-title":"Detection of altered T helper 1 and T helper 2 cytokine production by peripheral blood mononuclear cells in patients with multiple sclerosis utilizing intracellular cytokine detection by flow cytometry and surface marker analysis","volume":"3","year":"1996","journal-title":"Clinical Diagnostic Laboratory Immunology"},{"key":"2026092304300681000_2026.09.12.750449v1.49","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1992.00530270079022"},{"key":"2026092304300681000_2026.09.12.750449v1.50","doi-asserted-by":"publisher","DOI":"10.1038\/icb.2014.15"},{"key":"2026092304300681000_2026.09.12.750449v1.51","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2003.10.035"},{"key":"2026092304300681000_2026.09.12.750449v1.52","doi-asserted-by":"crossref","unstructured":"Lee, M. , Lee, Y. , Song, J. , Lee, J. & Chang, S.-Y. Tissue-specific role of CX3CR1 expressing immune cells and their relationships with human disease. Immune network 18 (2018).","DOI":"10.4110\/in.2018.18.e5"},{"key":"2026092304300681000_2026.09.12.750449v1.53","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0413207"},{"key":"2026092304300681000_2026.09.12.750449v1.54","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3241-13.2013"},{"key":"2026092304300681000_2026.09.12.750449v1.55","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-015-1452-x"},{"key":"2026092304300681000_2026.09.12.750449v1.56","doi-asserted-by":"publisher","DOI":"10.1007\/s11481-018-09832-z"},{"key":"2026092304300681000_2026.09.12.750449v1.57","doi-asserted-by":"publisher","DOI":"10.1007\/s40263-021-00822-z"},{"key":"2026092304300681000_2026.09.12.750449v1.58","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0804477"},{"key":"2026092304300681000_2026.09.12.750449v1.59","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-5699(99)01512-1"},{"key":"2026092304300681000_2026.09.12.750449v1.60","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21939"},{"key":"2026092304300681000_2026.09.12.750449v1.61","doi-asserted-by":"publisher","DOI":"10.3390\/cells8101236"},{"key":"2026092304300681000_2026.09.12.750449v1.62","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-013-1112-y"},{"key":"2026092304300681000_2026.09.12.750449v1.63","doi-asserted-by":"publisher","DOI":"10.1007\/s12017-019-08551-9"},{"key":"2026092304300681000_2026.09.12.750449v1.64","doi-asserted-by":"publisher","DOI":"10.1039\/D1LC00030F"},{"key":"2026092304300681000_2026.09.12.750449v1.65","doi-asserted-by":"publisher","DOI":"10.1039\/D1LC00145K"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.09.12.750449","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T11:30:40Z","timestamp":1790163040000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.09.12.750449"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,18]]},"references-count":65,"URL":"https:\/\/doi.org\/10.64898\/2026.09.12.750449","relation":{},"subject":[],"published":{"date-parts":[[2026,9,18]]},"subtype":"preprint"}}