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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / drug effects
  • Cells, Cultured
  • Clemastine / pharmacology
  • Drug Evaluation, Preclinical / methods
  • Female
  • High-Throughput Screening Assays / methods*
  • Histamine H1 Antagonists / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Multiple Sclerosis / drug therapy*
  • Muscarinic Antagonists / isolation & purification*
  • Muscarinic Antagonists / pharmacology
  • Nanostructures
  • Nerve Fibers, Myelinated / drug effects*
  • Oligodendroglia / cytology
  • Oligodendroglia / drug effects
  • Oligodendroglia / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Regeneration / drug effects


  • Histamine H1 Antagonists
  • Muscarinic Antagonists
  • Clemastine