Blood brain barrier (BBB) models are essential to study the transport efficacy of drugs that target brain and to understand the pathological neurovascular functions in various diseases. Despite the high complexity and high cost of in vivo animal BBB models, 80% of drug candidates that cleared the animal tests failed subsequently in the clinical trials. Therefore, a highly robust, predictive and cost-effective in vitro BBB models is needed. To address this issue, microfluidic technology is utilized to create a 3D BBB model through the co-culture of human induced pluripotent stem cell (iPSC)-derived endothelial cells (EC), brain pericytes (PC) and astrocytes (AC). These all human cells rearrange themselves and form microvascular network within a fibrin gel through vasculogenesis. The BBB model not only exhibits physiologically relevant structures such as the expression of tight junction proteins, more importantly it also has permeability that is comparable to in vivo measurement in rat brain. This in vitro BBB model can therefore be used to screen for brain-targeting drugs or to study the neurovascular functions.
This protocol is based on work by Campisi et al in reference (1). We thank Dr. Marco Campisi for his contribution to the preparation of this document.
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- 3D self-organized microvascular model of the human blood-brain barrier with endothelial cells, pericytes and astrocytes. Campisi M, Shin YJ, Osaki T, Hajal C, Chiono V, Kamm RD. Biomaterials 12 July 2018 https://doi.org/10.1016/j.biomaterials.2018.07.014
- A 3D neurovascular microfluidic model consisting of neurons, astrocytes and cerebral endothelial cells as blood-brain barrier. Adriani G, Ma DL, Pavesi A, Kamm R, Goh ELK. Lab Chip, 2016. 17 (3):448-459