Advancements in modelling human blood brain-barrier on a chip DOI Creative Commons

Vita Guarino,

Alessandra Zizzari, Monica Bianco

et al.

Biofabrication, Journal Year: 2023, Volume and Issue: 15(2), P. 022003 - 022003

Published: Jan. 23, 2023

Abstract The human Blood Brain Barrier (hBBB) is a complex cellular architecture separating the blood from brain parenchyma. Its integrity and perfect functionality are essential for preventing neurotoxic plasma components pathogens enter brain. Although vital preserving correct activity, low permeability of hBBB represents huge impediment to treat mental neurological disorders or address tumors. Indeed, vast majority potential drug treatments unable reach crossing hBBB. On other hand, can be damaged its increase as result infections in presence neurodegenerative diseases. Current vitro systems vivo animal models used study molecular/drug transport mechanism through have several intrinsic limitations that difficult overcome. In this scenario, Organ-on-Chip (OoC) based on microfluidic technologies considered promising innovative platforms combine handiness an model with complexity living organ, while reducing time costs. review, we focus recent advances OoCs developing models, aim providing reader critical overview main guidelines design manufacture hBBB-on-chip, whose compartments need mimic ‘blood side’ ‘brain barrier, choose cells types both representative convenient, adequately evaluate barrier integrity, stability, functionality.

Language: Английский

Selenium at the Neural Barriers: AReview DOI Creative Commons
Nikolay Solovyev, Evgenii Drobyshev, Bastian Blume

et al.

Frontiers in Neuroscience, Journal Year: 2021, Volume and Issue: 15

Published: Feb. 5, 2021

Selenium (Se) is known to contribute several vital physiological functions in mammals: antioxidant defense, fertility, thyroid hormone metabolism, and immune response. Growing evidence indicates the crucial role of Se Se-containing selenoproteins brain function. As for other essential trace elements, dietary needs reach effective concentrations central nervous system (CNS) exert its functions. To do so, Se-species have cross blood–brain barrier (BBB) and/or blood–cerebrospinal fluid (BCB) choroid plexus. The main interface between general circulation body CNS BBB. Endothelial cells capillaries forming so-called tight junctions are primary anatomic units BBB, mainly responsible current review focuses on transport brain, primarily including selenoprotein P/low-density lipoprotein receptor-related protein 8 (LRP8, also as apolipoprotein E receptor-2) dependent pathway, supplementary routes into via low molecular weight Se-species. Additionally, potential BCB, neurovascular unit (NVU) discussed. Finally, perspectives regarding investigating gut-brain axis outlined.

Language: Английский

Citations

50

Modeling ischemic stroke in a triculture neurovascular unit on-a-chip DOI Creative Commons

Nienke R. Wevers,

Arya Lekshmi Nair,

Tania M. Fowke

et al.

Fluids and Barriers of the CNS, Journal Year: 2021, Volume and Issue: 18(1)

Published: Dec. 14, 2021

In ischemic stroke, the function of cerebral vasculature is impaired. This vascular structure formed by so-called neurovascular unit (NVU). A better understanding mechanisms involved in NVU dysfunction and recovery may lead to new insights for development highly sought therapeutic approaches. To date, there remains an unmet need complex human vitro models study events seen brain.We here describe a on-a-chip model using platform that allows culture 40 chips parallel. The comprises perfused vessel primary brain endothelial cells co-culture with induced pluripotent stem cell derived astrocytes neurons. Ischemic stroke was mimicked threefold approach combines chemical hypoxia, hypoglycemia, halted perfusion.Immunofluorescent staining confirmed expression adherens tight junction proteins, as well astrocytic neuronal markers. addition, expresses relevant transporters shows spontaneous firing. demonstrates barrier function, evidenced retention small molecule sodium fluorescein its lumen. Exposure toxic compound staurosporine disrupted barrier, causing reduced transepithelial electrical resistance increased permeability fluorescein. Under mimicking conditions, showed strongly (35-fold higher apparent permeability) 7.3-fold decreased mitochondrial potential. Furthermore, levels adenosine triphosphate were significantly on both blood- side (4.8-fold 11.7-fold reduction, respectively).The presented can be used fundamental studies other neurological diseases investigation potential restorative therapies fight disorders. Due platform's relatively high throughput compatibility automation, holds drug screening.

Language: Английский

Citations

47

Interstitial flow enhances the formation, connectivity, and function of 3D brain microvascular networks generated within a microfluidic device DOI
Max A. Winkelman,

Diana Y Kim,

Shravani Kakarla

et al.

Lab on a Chip, Journal Year: 2021, Volume and Issue: 22(1), P. 170 - 192

Published: Nov. 30, 2021

The bulk flow of interstitial fluid through tissue is an important factor in human biology, including the development brain microvascular networks (MVNs) with blood-brain barrier (BBB). Bioengineering perfused, functional MVNs has great potential for modeling neurovascular diseases and drug delivery. However, most vitro models do not implement during generation microvessels. Using a microfluidic device (MFD), we cultured primary endothelial cells (BECs), pericytes, astrocytes within 3D fibrin matrix (flow) without (static) flow. We found that was beneficial both BEC angiogenesis vasculogenesis. Brain under conditions achieved anastomosis were perfusable, whereas those static lacked connectivity ability to be perfused. Compared culture, microvessels developed culture exhibited enhanced vessel area, branch length diameter, connectivity, longevity. Although there no change pericyte coverage microvessels, slight increase astrocyte observed conditions. In addition, immunofluorescence intensity basal lamina proteins, collagen IV laminin, nearly doubled culture. Lastly, function conditions, as demonstrated by decreased dextran permeability. Taken together, these results highlighted importance perfused characteristics similar BBB.

Language: Английский

Citations

45

Heterocellular spheroids of the neurovascular blood-brain barrier as a platform for personalized nanoneuromedicine DOI Creative Commons
Murali Kumarasamy, Alejandro Sosnik

iScience, Journal Year: 2021, Volume and Issue: 24(3), P. 102183 - 102183

Published: Feb. 16, 2021

Nanoneuromedicine investigates nanotechnology to target the brain and treat neurological diseases. In this work, we biofabricated heterocellular spheroids comprising human microvascular endothelial cells, vascular pericytes astrocytes combined with primary cortical neurons microglia isolated from neonate rats. The structure function are characterized by confocal laser scanning light sheet fluorescence microscopy, electron western blotting, RNA sequencing. spheroid bulk is formed neural cells surface they upregulate key structural functional proteins of blood-brain barrier. These cellular constructs utilized preliminary screen permeability polymeric, metallic, ceramic nanoparticles (NPs). Findings reveal that penetration distribution patterns depend on NP type would play a role in pathway, highlighting promise platform investigate interaction different nanomaterials central nervous system nanomedicine, nanosafety nanotoxicology.

Language: Английский

Citations

42

Advancements in modelling human blood brain-barrier on a chip DOI Creative Commons

Vita Guarino,

Alessandra Zizzari, Monica Bianco

et al.

Biofabrication, Journal Year: 2023, Volume and Issue: 15(2), P. 022003 - 022003

Published: Jan. 23, 2023

Abstract The human Blood Brain Barrier (hBBB) is a complex cellular architecture separating the blood from brain parenchyma. Its integrity and perfect functionality are essential for preventing neurotoxic plasma components pathogens enter brain. Although vital preserving correct activity, low permeability of hBBB represents huge impediment to treat mental neurological disorders or address tumors. Indeed, vast majority potential drug treatments unable reach crossing hBBB. On other hand, can be damaged its increase as result infections in presence neurodegenerative diseases. Current vitro systems vivo animal models used study molecular/drug transport mechanism through have several intrinsic limitations that difficult overcome. In this scenario, Organ-on-Chip (OoC) based on microfluidic technologies considered promising innovative platforms combine handiness an model with complexity living organ, while reducing time costs. review, we focus recent advances OoCs developing models, aim providing reader critical overview main guidelines design manufacture hBBB-on-chip, whose compartments need mimic ‘blood side’ ‘brain barrier, choose cells types both representative convenient, adequately evaluate barrier integrity, stability, functionality.

Language: Английский

Citations

19