NeuroMolecular Medicine

, Volume 14, Issue 2, pp 112–118 | Cite as

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
Original Paper

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 of myelin sheaths. Our microfluidic platform allows 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/mm2 when compared to unstimulated controls (19.6 ± 3.0 vs. 3.6 ± 2.3 MBP+ segments/mm2). 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.

Keywords

Microfluidic device Myelination Electrical stimulation Oligodendrocyte 

Notes

Acknowledgments

This work was funded by US Department of Defense USAMRMC/TATRC/USAMRAA contracts W81XWH-08-2-0192, W81XWH-09-2-0186, W81XWH-10-BCRP-IDEA, and Maryland Stem Cell Research Fund.

Supplementary material

12017_2012_8170_MOESM1_ESM.docx (20 kb)
Supplementary material 1 (DOCX 19 kb)
12017_2012_8170_MOESM2_ESM.tif (10.7 mb)
Supplementary material 2 (TIFF 10953 kb)

Supplementary material 3 (AVI 8504 kb)

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • In Hong Yang
    • 1
    • 5
  • Devin Gary
    • 2
    • 3
  • Misti Malone
    • 1
    • 2
  • Stephen Dria
    • 1
  • Thierry Houdayer
    • 2
  • Visar Belegu
    • 2
    • 3
  • John W. Mcdonald
    • 2
    • 3
    • 4
  • Nitish Thakor
    • 1
    • 5
  1. 1.Department of Biomedical Engineering, School of MedicineJohns Hopkins UniversityBaltimoreUSA
  2. 2.The International Center for Spinal Cord Injury, Hugo Moser Research InstituteKennedy Krieger InstituteBaltimoreUSA
  3. 3.Department of Neurology, School of MedicineJohns Hopkins UniversityBaltimoreUSA
  4. 4.Department of Physical Medicine and Rehabilitation, School of MedicineJohns Hopkins UniversityBaltimoreUSA
  5. 5.SiNAPSENational University of SingaporeSingaporeSingapore

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