4.6 Article

A neurovascular unit-on-a-chip: culture and differentiation of human neural stem cells in a three-dimensional microfluidic environment

Journal

NEURAL REGENERATION RESEARCH
Volume 17, Issue 10, Pages 2260-2266

Publisher

WOLTERS KLUWER MEDKNOW PUBLICATIONS
DOI: 10.4103/1673-5374.337050

Keywords

(neural) differentiation; astrocyte; blood-brain barrier; brain microvascular endothelial cells; central nervous system; microfluidics; neural stem cells; neuron; neurovascular unit; oligodendrocyte; organ-on-a-chip

Funding

  1. Stem Cell Clinical Research Project of China [CMR-20161129-1003]
  2. Liaoning Province Excellent Talent Program Project of China [XLYC1902031]
  3. Dalian Innovation Technology Foundation of China [2018J11CY025]

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Traditional cell cultures do not accurately reflect the complex functional characteristics of human tissues and organs, but microfluidic technology combined with multipotential differentiation of neural stem cells has established an in vitro model of a functionalized neurovascular unit. This model can be used in central nervous system disease research and drug development.
Biological studies typically rely on a simple monolayer cell culture, which does not reflect the complex functional characteristics of human tissues and organs, or their real response to external stimuli. Microfluidic technology has advantages of high-throughput screening, accurate control of the fluid velocity, low cell consumption, long-term culture, and high integration. By combining the multipotential differentiation of neural stem cells with high throughput and the integrated characteristics of microfluidic technology, an in vitro model of a functionalized neurovascular unit was established using human neural stem cell-derived neurons, astrocytes, oligodendrocytes, and a functional microvascular barrier. The model comprises a multi-layer vertical neural module and vascular module, both of which were connected with a syringe pump. This provides controllable conditions for cell inoculation and nutrient supply, and simultaneously simulates the process of ischemic/hypoxic injury and the process of inflammatory factors in the circulatory system passing through the blood-brain barrier and then acting on the nerve tissue in the brain. The in vitro functionalized neurovascular unit model will be conducive to central nervous system disease research, drug screening, and new drug development.

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