Axon Myelination and Electrical Stimulation in a Microfluidic, Compartmentalized Cell Culture Platform

作者：Yang In Hong; Gary Devin; Malone Misti; Dria Stephen; Houdayer Thierry; Belegu Visar; Mcdonald John W; Thakor Nitish^*

来源：NeuroMolecular Medicine, 2012, 14(2): 112-118.

DOI：10.1007/s12017-012-8170-5

• Microfluidic device
• Myelination
• Electrical stimulation
• Oligodendrocyte

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 similar to 190 ka"broken vertical bar 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 +/- A 3.0 vs. 3.6 +/- A 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.

• 出版日期2012-6