Theme: Microphysiological Systems - Developmental Neurobiology Models of the Central Nervous System (CNS)

Proper functioning of the central nervous system (CNS) is critically dependent on various forms of signaling among multiple neural cell types during the developmental process. For example, the formation of multilayered myelin sheaths around axons by oligodendrocytes is critical for rapid nerve impulse conduction in the CNS. Dysfunction of oligodendrocytes and/or loss of myelin sheaths result in major neurological disorders such as multiple sclerosis, schizophrenia, and Alzheimer’s disease. However, conventional two-dimensional (2D) dissociated cell culture method has not yet been successful in recapitulating major CNS developmental events. This, together with the lack of suitable in vitro models, have been a major roadblock for the mechanistic understanding of the neurodevelopmental processes and developing efficient therapeutic targets/strategies. We are interested in developing technologies that can manipulate cells, cellular aggregates, and their microenvironment with unprecedented precision to provide culture environment that are more physiologically relevant, co-culture systems that can study and identify cell-cell interactions, and platforms that can be used for axon growth and regeneration analysis.

Neuron-Glia Co-Culture Microsystems
The function of vertebrate nervous system is critically dependent on the formation of insulating myelin sheaths around axons.  Myelination is a sequential, multi-step process that requires reciprocal signals between axons and myelin-producing cells – oligodendrocytes in the central nervous system (CNS) and Schwann cells in the peripheral nervous system (PNS).  Dysfunction of myelin-forming cells and/or loss of myelin sheath underline many neurological disorders including multiple sclerosis, periventricular leukomalacia, Alzheimer’s disease and psychological disorders such as schizophrenia.  Despite recent progress in understanding the molecular signals in PNS myelination, the signals that regulate myelination in the mammalian CNS remain largely unknown.  This is in part due to the complexity of the CNS myelination process and lack of appropriate in vitro CNS myelination models that are easily accessible for experimental manipulations. We are employing an innovative multidisciplinary approach to establish a novel CNS myelination co-culture microsystem that provides a powerful means to study axon-glia communications during myelinogenesis. 

Funding Agency: National Institutes of Health (NIH) / National Instutite of Mental Health (NIMH)

- J. Park, H. Koito, J. Li, and A. Han, "Multi-Compartment Neuron-Glia Co-Culture Platform for Localized CNS Axon-Glia Interaction Study," Lab Chip, Vol. 12, pp. 3296-3304, 2012 (published as back cover).
- J. Park, J. Li, and A. Han, “Micro-Macro Hybrid Soft-lithography Master (MMHSM) Fabrication for Lab-on-a-chip Applications,” Biomedical Microdevices, Vol. 12, pp. 345-351, 2010.
- J. Park, H. Koito, J. Li, and A. Han, "Microfluidic Compartmentalized Co-culture Platform for CNS Axon Meylination Research," Biomedical Microdevices, Vol. 11, pp. 1145-1153, 2009.
- J. Park, H. Koito, J. Li, and A. Han, "A Multi-Compartment CNS Neuron-Glia Co-Culture Microfluidic Platform," Journal of Visualized Experiments, Vol. 31, http://www.jove.com/index/Details.stp?ID=1399, 2009.

3D Neural Microphysiological Systems
The goal of our research is to develop a microfluidic in vitro 3D CNS neural stem/progenitor cell (NSPC) aggregate platform to recapitulate major neural development processes in vitro.  Microfluidics and lab-on-a-chip approaches will be the enabling technology for this development.

- J. Park, S. Kim, J. Li, and A. Han, "In Vitro Microphysiological Systems of CNS Neurons,"1st Annual IEEE EMBS Micro and Nanotechnology in Medicine Conference, Ka'anapali, HI, 2012.
- J. Park, H. Koito, J. Li, and A. Han, "Neuron Aggregate Culture Platform for in vitro CNS Myelination Study,"14th International Conference on Miniaturized Systems for Chemistry and Life Sciences, pp. 46-48, Groningen, The Netherlands, 2010.

Quantitative Axon Growth Analysis Platform
Growth capability of neurons is an essential factor in axon regeneration.  To better understand how microenvironments influence axon growth, methods that allow spatial control of cellular microenvironments and easy quantification of axon growth are critically needed.  We are developing a microchip capable of physical and fluidic isolation of axons from neuronal somata and dendrites that enables localized biomolecular treatments and linear axon growth. 

- S. Kim, J. Park, A. Han, and J. Li, “Microfluidic Systems for Axonal Growth and Regeneration Research,” Neural Regeneration Research, Vol. 9 (19), pp. 1703-1705, 2014 - J. Park, S. Kim, S. I. Park, Y. Choe, J. Li, and A. Han, “A Microchip for Quantitative Analysis of CNS Axon Growth under Localized Biomolecular Treatments,” J. Neuroscience Methods, Vol. 21, pp. 166-174, 2014

Support for the NanoBio Systems Lab.