@article{bibcite_1166,
  keywords = {Transwell, blood-brain barrier (BBB), human immortalized cell lines, in vitro, neurovascular unit (NVU) model},
  author = {Chiara Barberio and Aimee Withers and Yash Mishra and Pierre-Olivier Couraud and Ignacio A. Romero and Babette Weksler and R{\'o}is{\'\i}n M. Owens},
  title = {A human-derived neurovascular unit in vitro model to study the effects of cellular cross-talk and soluble factors on barrier integrity},
  abstract = {The blood-brain barrier (BBB) restricts paracellular and transcellular diffusion of compounds and is part of a dynamic multicellular structure known as the "neurovascular unit" (NVU), which strictly regulates the brain homeostasis and microenvironment. Several neuropathological conditions (e.g., Parkinson{\textquoteright}s disease and Alzheimer{\textquoteright}s disease), are associated with BBB impairment yet the exact underlying pathophysiological mechanisms remain unclear. In total, 90\% of drugs that pass animal testing fail human clinical trials, in part due to inter-species discrepancies. Thus, in vitro human-based models of the NVU are essential to better understand BBB mechanisms; connecting its dysfunction to neuropathological conditions for more effective and improved therapeutic treatments. Herein, we developed a biomimetic tri-culture NVU in vitro model consisting of 3 human-derived cell lines: human cerebral micro-vascular endothelial cells (hCMEC/D3), human 1321N1 (astrocyte) cells, and human SH-SY5Y neuroblastoma cells. The cells were grown in Transwell hanging inserts in a variety of configurations and the optimal setup was found to be the comprehensive tri-culture model, where endothelial cells express typical markers of the BBB and contribute to enhancing neural cell viability and neurite outgrowth. The tri-culture configuration was found to exhibit the highest transendothelial electrical resistance (TEER), suggesting that the cross-talk between astrocytes and neurons provides an important contribution to barrier integrity. Lastly, the model was validated upon exposure to several soluble factors [e.g., Lipopolysaccharides (LPS), sodium butyrate (NaB), and retinoic acid (RA)] known to affect BBB permeability and integrity. This in vitro biological model can be considered as a highly biomimetic recapitulation of the human NVU aiming to unravel brain pathophysiology mechanisms as well as improve testing and delivery of therapeutics.},
  year = {2022},
  journal = {Frontiers in Cellular Neuroscience},
  volume = {16},
  pages = {1065193},
  month = {2022},
  issn = {1662-5102},
  doi = {10.3389/fncel.2022.1065193},
  language = {eng},
}