Lab-on-a-chip device integrating a human stem cell-based blood-brain barrier model with neural organoids for translational research
- 1Institute of Biophysics, HUN-REN Biological Research Centre, 6726 Szeged, Hungary
Abstract
For advanced biomedical research, complex, well-described human blood-brain barrier (BBB) models are crucial for studying central nervous system pathologies and brain targeting of nanotherapeutics. Our aim was to establish and characterize a complex lab-on-a-chip (LOC) system integrating a BBB model with neural organoids (NO). We optimized the conditions for BBB-NO models under static and dynamic circumstances. The combination of a human stem cell-derived BBB co-culture model with human midbrain organoids in a microfluidic LOC allowed the observation of BBB and neural tissue changes and the separate analysis of the barrier and brain units. The LOC design enabled phase contrast and fluorescent microscopy on the whole brain endothelial culture surface, barrier integrity and permeability measurements across the BBB model, and molecule passage into NOs. BBB-specific endothelial morphology, gene and protein expression, and good barrier integrity were demonstrated, corroborating the strength of the LOC engineering and cellular design. The transport of targeted nanoparticles across the BBB model followed by their entry to neural organoids validated the barrier integrity and transporter functionality of the dynamic integrated complex model. As a proof-of-concept experiment to confirm the translational value of the BBB-NO model integrated in the LOC device, we examined a clinically used hyperosmolar iodinated contrast agent, iopamidol, with confirmed neurological side effects. We corroborated that iopamidol induces transient BBB dysfunction and neural effects in the complex system, not only validating the complex dynamic BBB-NO model but also pointing to the necessity to study BBB changes together with NO functions.
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BibTeX
@misc{vigh2026labonachip,
title = {{Lab-on-a-chip device integrating a human stem cell-based blood-brain barrier model with neural organoids for translational research}},
author = {J. P. Vigh and A. E. Kocsis and A. R. Santa-Maria and N. Kucsapszky and E. Bato and S. Bolognin and J. C. Schwamborn and A. Kincses and S. Valkai and A. Szecsko and S. Veszelka and M. Maria and G. Porkolab and T. H. M. Phan and J.-S. Jan and R. Wirth and Z. Szabo and M. Culot and Y. Morofuji and A. Der and M. A. Deli and F. R. Walter},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.15.750866},
url = {https://www.biorxiv.org/content/10.64898/2026.09.15.750866v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Lab-on-a-chip device integrating a human stem cell-based blood-brain barrier model with neural organoids for translational research
AU - J. P. Vigh
AU - A. E. Kocsis
AU - A. R. Santa-Maria
AU - N. Kucsapszky
AU - E. Bato
AU - S. Bolognin
AU - J. C. Schwamborn
AU - A. Kincses
AU - S. Valkai
AU - A. Szecsko
AU - S. Veszelka
AU - M. Maria
AU - G. Porkolab
AU - T. H. M. Phan
AU - J.-S. Jan
AU - R. Wirth
AU - Z. Szabo
AU - M. Culot
AU - Y. Morofuji
AU - A. Der
AU - M. A. Deli
AU - F. R. Walter
PY - 2026
DA - 2026/09/15
PB - bioRxiv
DO - 10.64898/2026.09.15.750866
UR - https://www.biorxiv.org/content/10.64898/2026.09.15.750866v1
AB - For advanced biomedical research, complex, well-described human blood-brain barrier (BBB) models are crucial for studying central nervous system pathologies and brain targeting of nanotherapeutics. Our aim was to establish and characterize a complex lab-on-a-chip (LOC) system integrating a BBB model with neural organoids (NO). We optimized the conditions for BBB-NO models under static and dynamic circumstances. The combination of a human stem cell-derived BBB co-culture model with human midbrain organoids in a microfluidic LOC allowed the observation of BBB and neural tissue changes and the separate analysis of the barrier and brain units. The LOC design enabled phase contrast and fluorescent microscopy on the whole brain endothelial culture surface, barrier integrity and permeability measurements across the BBB model, and molecule passage into NOs. BBB-specific endothelial morphology, gene and protein expression, and good barrier integrity were demonstrated, corroborating the strength of the LOC engineering and cellular design. The transport of targeted nanoparticles across the BBB model followed by their entry to neural organoids validated the barrier integrity and transporter functionality of the dynamic integrated complex model. As a proof-of-concept experiment to confirm the translational value of the BBB-NO model integrated in the LOC device, we examined a clinically used hyperosmolar iodinated contrast agent, iopamidol, with confirmed neurological side effects. We corroborated that iopamidol induces transient BBB dysfunction and neural effects in the complex system, not only validating the complex dynamic BBB-NO model but also pointing to the necessity to study BBB changes together with NO functions.
ER -