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Micropillar arrays as a high-throughput screening platform for therapeutics in multiple sclerosis

Mei, Feng ; Fancy, Stephen P J ; Shen, Yun-An A ; Niu, Jianqin ; Zhao, Chao ; Presley, Bryan ; Miao, Edna ; Lee, Seonok ; Mayoral, Sonia R ; Redmond, Stephanie A ; Etxeberria, Ainhoa ; Xiao, Lan ; Franklin, Robin J M ; Green, Ari ; Hauser, Stephen L ; Chan, Jonah R

Nature medicine, 2014-08, Vol.20 (8), p.954-960 [Periódico revisado por pares]

United States: Nature Publishing Group

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Título:
Micropillar arrays as a high-throughput screening platform for therapeutics in multiple sclerosis
Autor: Mei, Feng ; Fancy, Stephen P J ; Shen, Yun-An A ; Niu, Jianqin ; Zhao, Chao ; Presley, Bryan ; Miao, Edna ; Lee, Seonok ; Mayoral, Sonia R ; Redmond, Stephanie A ; Etxeberria, Ainhoa ; Xiao, Lan ; Franklin, Robin J M ; Green, Ari ; Hauser, Stephen L ; Chan, Jonah R
Assuntos: Analysis ; Animals ; Arrays ; Axonogenesis ; Axons ; Biological activity ; Care and treatment ; Cell differentiation ; Cell Differentiation - drug effects ; Cells, Cultured ; Clemastine - pharmacology ; Diagnosis ; Differentiation ; Drug development ; Drug discovery ; Drug Evaluation, Preclinical - methods ; Drug screening ; Female ; High-throughput screening ; High-throughput screening (Biochemical assaying) ; High-Throughput Screening Assays - methods ; Histamine H1 Antagonists - pharmacology ; Image acquisition ; Image enhancement ; Medical screening ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Multiple sclerosis ; Multiple Sclerosis - drug therapy ; Muscarinic Antagonists - isolation & purification ; Muscarinic Antagonists - pharmacology ; Myelin ; Myelination ; Nanostructures ; Nerve Fibers, Myelinated - drug effects ; Oligodendroglia - cytology ; Oligodendroglia - drug effects ; Oligodendroglia - physiology ; Rats ; Rats, Sprague-Dawley ; Regeneration - drug effects ; Rodents ; Screening
É parte de: Nature medicine, 2014-08, Vol.20 (8), p.954-960
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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Descrição: 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.
Editor: United States: Nature Publishing Group
Idioma: Inglês

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Micropillar arrays as a high-throughput screening platform for therapeutics in multiple sclerosis

Mei, Feng ; Fancy, Stephen P J ; Shen, Yun-An A ; Niu, Jianqin ; Zhao, Chao ; Presley, Bryan ; Miao, Edna ; Lee, Seonok ; Mayoral, Sonia R ; Redmond, Stephanie A ; Etxeberria, Ainhoa ; Xiao, Lan ; Franklin, Robin J M ; Green, Ari ; Hauser, Stephen L ; Chan, Jonah R

United States: Nature Publishing Group

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