title: Micropillar arrays as a high-throughput screening platform for therapeutics in multiple sclerosis.
abstract: Functional screening for compounds that promote remyelination represents a major hurdle in the development of rational therapeutics for multiple sclerosis. Screening for remyelination is problematic, as myelination requires the presence of axons. Standard methods do not resolve cell-autonomous effects and are not suited for high-throughput formats. Here we describe a binary indicant for myelination using micropillar arrays (BIMA). Engineered with conical dimensions, micropillars permit resolution of the extent and length of membrane wrapping from a single two-dimensional image. Confocal imaging acquired from the base to the tip of the pillars allows for detection of concentric wrapping observed as 'rings' of myelin. The platform is formatted in 96-well plates, amenable to semiautomated random acquisition and automated detection and quantification. Upon screening 1,000 bioactive molecules, we identified a cluster of antimuscarinic compounds that enhance oligodendrocyte differentiation and remyelination. Our findings demonstrate a new high-throughput screening platform for potential regenerative therapeutics in multiple sclerosis.
authors.affiliation: Department of Neurology and Program in Neuroscience, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Mei
authors.affiliation: Department of Neurology and Program in Neuroscience, University of California, San Francisco, San Francisco, California, USA.|Department of Pediatrics, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Stephen P J
authors.initials: SPJ
authors.lastname: Fancy
authors.affiliation: Department of Neurology and Program in Neuroscience, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Yun-An A
authors.initials: YA
authors.lastname: Shen
authors.affiliation: Department of Histology and Embryology, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Chongqing, China.
authors.forename: Jianqin
authors.initials: J
authors.lastname: Niu
authors.affiliation: Wellcome Trust Medical Research Council, Cambridge Stem Cell Institute and Department of Veterinary Medicine, University of Cambridge, Cambridge, UK.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Trianja Technologies, Allen, Texas, USA.
authors.forename: Bryan
authors.initials: B
authors.lastname: Presley
authors.affiliation: Department of Neurology and Program in Neuroscience, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Edna
authors.initials: E
authors.lastname: Miao
authors.affiliation: Department of Neurology and Program in Neuroscience, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Seonok
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Neurology and Program in Neuroscience, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Sonia R
authors.initials: SR
authors.lastname: Mayoral
authors.affiliation: Department of Neurology and Program in Neuroscience, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Redmond
authors.affiliation: Department of Neurology and Program in Neuroscience, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Ainhoa
authors.initials: A
authors.lastname: Etxeberria
authors.affiliation: Department of Histology and Embryology, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Chongqing, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Xiao
authors.affiliation: Wellcome Trust Medical Research Council, Cambridge Stem Cell Institute and Department of Veterinary Medicine, University of Cambridge, Cambridge, UK.
authors.forename: Robin J M
authors.initials: RJM
authors.lastname: Franklin
authors.affiliation: Department of Neurology and Program in Neuroscience, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Ari
authors.initials: A
authors.lastname: Green
authors.affiliation: Department of Neurology and Program in Neuroscience, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Hauser
authors.affiliation: Department of Neurology and Program in Neuroscience, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Jonah R
authors.initials: JR
authors.lastname: Chan
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D002974:Clemastine / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D057166:High-Throughput Screening Assays / Q000379:methods*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009103:Multiple Sclerosis / Q000188:drug therapy*; D018727:Muscarinic Antagonists / Q000302:isolation & purification* / Q000494:pharmacology; D049329:Nanostructures; D009413:Nerve Fibers, Myelinated / Q000187:drug effects*; D009836:Oligodendroglia / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration / Q000187:drug effects
chemical_list: D006634:Histamine H1 Antagonists; D018727:Muscarinic Antagonists; D002974:Clemastine