Neural Regeneration Research ›› 2022, Vol. 17 ›› Issue (10): 2260-2266.doi: 10.4103/1673-5374.337050

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

Wen-Juan Wei1, 2, Ya-Chen Wang1, 2, Xin Guan1, 2, Wei-Gong Chen1, 2, Jing Liu1, 2   

  1. 1Stem Cell Clinical Research Center, National Joint Engineering Laboratory, Regenerative Medicine Center, the First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, China; 2Dalian Innovation Institute of Stem Cell and Precision Medicine, Dalian, Liaoning Province, China
  • Online:2022-10-15 Published:2022-03-16
  • Contact: Jing Liu, PhD, liujing.dlrmc@hotmail.com.
  • Supported by:
    This study was supported by the Stem Cell Clinical Research Project of China, No. CMR-20161129-1003; Liaoning Province Excellent Talent Program Project of China, No. XLYC1902031; and the Dalian Innovation Technology Foundation of China, No. 2018J11CY025 (all to JL).

Abstract: 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.

Key words: (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