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Nat Med. 2014 Aug;20(8):954-960. doi: 10.1038/nm.3618. Epub 2014 Jul 6.

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

Author information

1
Department of Neurology and Program in Neuroscience, University of California, San Francisco, San Francisco, California, USA.
2
Department of Pediatrics, University of California, San Francisco, San Francisco, California, USA.
3
Department of Histology and Embryology, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Chongqing, China.
4
Wellcome Trust Medical Research Council, Cambridge Stem Cell Institute and Department of Veterinary Medicine, University of Cambridge, Cambridge, UK.
5
Trianja Technologies, Allen, Texas, USA.
#
Contributed equally

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.

PMID:
24997607
PMCID:
PMC4830134
DOI:
10.1038/nm.3618
[Indexed for MEDLINE]
Free PMC Article

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