ESR 2 vision / project

ESR 2: 2 February 2021

In vitro models of the blood-brain and blood-CSF barriers using an integrated microfluidic device

Project Results

Models of brain barriers are important to study physiological functions, transport mechanisms, drug delivery and pathologies. Microfluidic and microelectronic integrated biochips are new tools to monitor several of the crucial parameters of cell-culture-based brain barrier models. We further developed a lab-on-a-chip device designed by our team (Walter et al. 2016) to model blood-brain and blood-cerebrospinal fluid barriers. The device allows co-culture of two or three types of cells, flow of culture medium, visualization of the entire cell layer by microscopy, real-time transcellular electrical resistance monitoring, and permeability measurements. The design of the chip was improved. A chip manufacturing protocol was established together with an individual registry system for each biochip to allow follow up, reproducibility and easy problem solving. Experiments were performed on a human brain endothelial cell line in the biochips to monitor the effect of fluid flow on resistance and other electrical parameters. In cooperation with UART, a stem cell derived human endothelial cell and bovine pericyte co-culture model (Cecchelli et al. 2014) was also tested in the biochip. The barrier tightening effect of fluid flow/shear stress was confirmed on both human cell-based blood-brain barrier models in the new version of the biochip. In addition, we investigated the role of glycocalyx and negative surface charge in blood-brain barrier permeability, and modulated the surface charge of brain endothelial cells with different methods.

Awards

2019	Finalist in the national Famelab in Hungary
2019	Best presentation in the PhD Journal Club course at the University of Szeged
2019	Best presenter in the international conference “International Student Congress of (Bio) Medical Sciences”, Groningen, Netherlands
2019	MCAA Micro grant to attend to “International Student Congress of (Bio) Medical Sciences”, Groningen, Netherlands
2018	Straub Young Scientist Prize, Biological Research Centre, Szeged, Hungary
2018	Special Prize at the 21st International Symposium on Signal Transduction at the BBB
2017	Best poster prize at the Hungarian Biophysics Conference, Szeged, Hungary

Outreach Experience

2019	Project manager, “NativeScientist” project, Hungary

Title of PhD thesis

The role of brain endothelial surface charge and glycocalyx in the function and integrity of the blood-brain barrier

Current position (from 15 March 2022)

Postdoctoral fellow Brain Targeting Program, Wyss Institute for Biologically Inspired Engineering, Harvard University Center for Life Science

BtRAIN publications

Walter FR, Santa-Maria AR, Mészáros M, Veszelka S, Dér A, Deli MA. Surface charge, glycocalyx, and blood-brain barrier function. Tissue Barriers. 2021 Jul 3;9(3):1904773. doi: 10.1080/21688370.2021.1904773.

Santa-Maria AR, Walter FR, Figueiredo R, Kincses A, Vigh JP, Heymans M, Culot M, Winter P, Gosselet F, Dér A, Deli MA. Flow induces barrier and glycocalyx-related genes and negative surface charge in a lab-on-a-chip human blood-brain barrier model. J Cereb Blood Flow Metab. 2021 Sep;41(9):2201-2215. doi: 10.1177/0271678X21992638.

Kincses A, Santa-Maria AR, Walter FR, Dér L, Horányi N, Lipka DV, Valkai S, Deli MA, Dér A. A chip device to determine surface charge properties of confluent cell monolayers by measuring streaming potential. Lab Chip. 2020 Oct 21;20(20):3792-3805. doi: 10.1039/d0lc00558d.

Kanyo N, Kovacs KD, Saftics A, Szekacs I, Peter B, Santa-Maria AR, Walter FR, Dér A, Deli MA, Horvath R. Glycocalyx regulates the strength and kinetics of cancer cell adhesion revealed by biophysical models based on high resolution label-free optical data. Sci Rep. 2020 Dec 30;10(1):22422. doi: 10.1038/s41598-020-80033-6.

Santa-Maria AR, Heymans M, Walter FR, Culot M, Gosselet F, Deli MA, Neuhaus W. Transport Studies Using Blood-Brain Barrier In Vitro Models: A Critical Review and Guidelines. Handb Exp Pharmacol. 2020 Oct 11. doi: 10.1007/164_2020_394.

Gróf I, Bocsik A, Harazin A, Santa-Maria AR, Vizsnyiczai G, Barna L, Kiss L, Fűr G, Rakonczay Z Jr, Ambrus R, Szabó-Révész P, Gosselet F, Jaikumpun P, Szabó H, Zsembery Á, Deli MA. The Effect of Sodium Bicarbonate, a Beneficial Adjuvant Molecule in Cystic Fibrosis, on Bronchial Epithelial Cells Expressing a Wild-Type or Mutant CFTR Channel. Int J Mol Sci. 2020 Jun 4;21(11):4024. doi: 10.3390/ijms21114024.

Santa-Maria AR, Walter FR, Valkai S, Brás AR, Mészáros M, Kincses A, Klepe A, Gaspar D, Castanho MARB, Zimányi L, Dér A, Deli MA. Lidocaine turns the surface charge of biological membranes more positive and changes the permeability of blood-brain barrier culture models. Biochim Biophys Acta Biomembr. 2019 Sep 1;1861(9):1579-1591. doi: 10.1016/j.bbamem.2019.07.008.