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[Experimental Neurobiology] Flow Shear Stress Enhances the Proliferative Potential of Cultured Radia


Abstract:

Radial glial cells (RGCs) which function as neural stem cells are known to be non-excitable and their proliferation depends on the intracellular calcium (Ca2+) level. It has been well established that Inositol 1,4,5-trisphosphate (IP3)-mediated Ca2+ release and Ca2+ entry through various Ca2+ channels are involved in the proliferation of RGCs. Furthermore, RGCs line the ventricular wall and are exposed to a shear stress due to a physical contact with the cerebrospinal fluid (CSF). However, little is known about how the Ca2+ entry through mechanosensitive ion channels affects the proliferation of RGCs. Hence, we hypothesized that shear stress due to a flow of CSF boosts the proliferative potential of RGCs possibly via an activation of mechanosensitive Ca2+ channel during the embryonic brain development. Here, we developed a new microfluidic two-dimensional culture system to establish a link between the flow shear stress and the proliferative activity of cultured RGCs. Using this microfluidic device, we successfully visualized the artificial CSF and RGCs in direct contact and found a significant enhancement of proliferative capacity of RGCs in response to increased shear stress. To determine if there are any mechanosensitive ion channels involved, a mechanical stimulation by poking was given to individual RGCs. We found that a poking on radial glial cell induced an increase in intracellular Ca2+ level, which disappeared under the extracellular Ca2+-free condition. Our results suggest that the shear stress by CSF flow possibly activates mechanosensitive Ca2+ channels, which gives rise to a Ca2+ entry which enhances the proliferative capacity of RGCs.

Min Gu Park,1,2,3,† Heeyeong Jang,5,† Sang-Hoon Lee,1,4,5 and C. Justin Lee1,2,3 1KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul 02841, Korea. 2Center for Neuroscience and Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea. 3Center for Glia-Neuron Interaction, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea. 4School of Biomedical Engineering, College of Health Science, Korea University, Seoul 02841, Korea. 5Department of Bio-convergence Engineering, College of Health Science, Korea University, Seoul 02841, Korea.

To whom correspondence should be addressed. TEL: 82-2-958-6421, FAX: 82-2-958-6919, Email: cjl@kist.re.kr †These authors contributed equally to this work.

Received March 21, 2017; Revised April 05, 2017; Accepted April 05, 2017.

Link: https://en-journal.org/DOIx.php?id=10.5607/en.2017.26.2.71

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