Axon myelination and electrical stimulation in a microfluidic, compartmentalized cell culture platform

In Hong Yang, Devin Gary, Misti Malone, Stephen Dria, Thierry Houdayer, Visar Belegu, John W. McDonald, Nitish Thakor

Research output: Contribution to journalArticlepeer-review

Abstract

Axon demyelination contributes to the loss of sensory and motor function following injury or disease in the central nervous system. Numerous reports have demonstrated that myelination can be achieved in neuron/oligodendrocyte co-cultures.However, the ability to selectively treat neuron or oligodendrocyte (OL) cell bodies in co-cultures improves the value of these systems when designing mechanism-based therapeutics. We have developed a microfluidic-based compartmentalized culture system to achieve segregation of neuron and OL cell bodies while simultaneously allowing the formation ofmyelin sheaths. Ourmicrofluidic platformallows for a high replicate number, minimal leakage, and high flexibility. Using a custom built lid, fit with platinum electrodes for electrical stimulation (10-Hz pulses at a constant 3 V with ∼190 kΩ impedance), we employed the microfluidic platform to achieve activity-dependent myelin segment formation. Electrical stimulation of dorsal root ganglia resulted in a fivefold increase in the number of myelinated segments/mm 2 when compared to unstimulated controls (19.6 ± 3.0 vs. 3.6 ± 2.3 MBP + segments/mm 2). This work describes the modification of a microfluidic, multi-chamber system so that electrical stimulation can be used to achieve increased levels of myelination while maintaining control of the cell culture microenvironment.

Original languageEnglish (US)
Pages (from-to)112-118
Number of pages7
JournalNeuromolecular medicine
Volume14
Issue number2
DOIs
StatePublished - Jun 1 2012

Keywords

  • Electrical stimulation
  • Microfluidic device
  • Myelination
  • Oligodendrocyte

ASJC Scopus subject areas

  • Molecular Medicine
  • Neurology
  • Cellular and Molecular Neuroscience

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