In vitro blood brain barrier models: An overview

Jagtiani, Ekta; Yeolekar, Mihika; Naik, Shivraj; Patravale, Vandana

doi:10.1016/j.jconrel.2022.01.011

Cited by 46 publications

(37 citation statements)

References 132 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nevertheless, the model we chose has several advantages: ease to handle, low cost, rapidity, and experimental reproducibility [ 75 , 76 ]. Therefore, for our study, we reasoned that it would have been suitable to gain insights of our novel nanoformulation capability to overcome or not the BBB barrier.…”

Section: Discussionmentioning

confidence: 99%

Bisdemethoxycurcumin (BDC)-Loaded H-Ferritin-Nanocages Mediate the Regulation of Inflammation in Alzheimer’s Disease Patients

Gagliardi¹,

Truffi

Tinelli

et al. 2022

IJMS

View full text Add to dashboard Cite

Background: Bisdemethoxycurcumin (BDC) might be an inflammation inhibitor in Alzheimer’s Disease (AD). However, BDC is almost insoluble in water, poorly absorbed by the organism, and degrades rapidly. We thus developed a new nanoformulation of BDC based on H-Ferritin nanocages (BDC-HFn). Methods: We tested the BDC-HFn solubility, stability, and ability to cross a blood–brain barrier (BBB) model. We tested the effect of BDC-HFn on AD and control (CTR) PBMCs to evaluate the transcriptomic profile by RNA-seq. Results: We developed a nanoformulation with a diameter of 12 nm to improve the solubility and stability. The comparison of the transcriptomics analyses between AD patients before and after BDC-HFn treatment showed a major number of DEG (2517). The pathway analysis showed that chemokines and macrophages activation differed between AD patients and controls after BDC-HFn treatment. BDC-HFn binds endothelial cells from the cerebral cortex and crosses through a BBB in vitro model. Conclusions: Our data showed how BDC-Hfn could improve the stability of BDC. Significant differences in genes associated with inflammation between the same patients before and after BDC-Hfn treatment have been found. Inflammatory genes that are upregulated between AD and CTR after BDC-HFn treatment are converted and downregulated, suggesting a possible therapeutic approach.

show abstract

Section: Discussionmentioning

confidence: 99%

Bisdemethoxycurcumin (BDC)-Loaded H-Ferritin-Nanocages Mediate the Regulation of Inflammation in Alzheimer’s Disease Patients

Gagliardi¹,

Truffi

Tinelli

et al. 2022

IJMS

View full text Add to dashboard Cite

show abstract

“…Transwell systems ( Figure 3A ) comprised two compartments separated by a semipermeable plastic membrane in which vertical diffusion occurs. This basic in vitro BBB culture model involves the growth of a monolayer of ECs in the luminal side of the Transwell flat insert membrane, which represents the “capillary blood”, whereas the well in which it is inserted represents the “brain” or abluminal side where astroglia cells are cultured ( Jagtiani et al, 2022 ). In these Transwell systems, endothelial and astroglia cells can be in contact or not.…”

Section: In Vitro Bbb Models Overviewmentioning

confidence: 99%

“…Because of the complexity of the in vivo BBB structure, simplified in vitro BBB models have been used to gain knowledge into designing biochemical strategies to allow the temporarily opening of the BBB for the efficient delivery of drugs to the CNS, and saving costs in pre-screening and experimental studies ( Santaguida et al, 2006 ; Mahaffey, 2012 ; He et al, 2014 ). The assessment of the BBB formation and its integrity in engineered in vitro models consider different structural, microenvironmental and functional aspects that were previously reported ( Bhalerao et al, 2020 ; Williams-Medina et al, 2021 ; Jagtiani et al, 2022 ). These include the formation of tight cellular junctions ( Machado, 2012 ; Banerjee et al, 2016 ; Destefano et al, 2018 ), and the expression of BBB markers such as von Willebrand Factor (vWF) and the protein cluster of endothelial cell differentiation 31 (CD31) ( Löscher and Potschka, 2005 ; Gil-Martins et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

“…The use of super-resolution imaging techniques as environmental scanning electron microscope (ESEM), structured illumination microscopy (SIM), stimulated emission depletion (STED) microscopy, and single molecule localization microscopy (SMLM) enables imaging tight and adherens junctions at the nanoscale, which appear as a network of contact points between extracellular claudins, occludins, and other transmembrane proteins ( Destefano et al, 2018 ; Gonschior et al, 2020 ). In the same way, the cell viability and junction proteins expression can be evaluated by immunocytochemistry using light-phase/confocal imaging ( Jagtiani et al, 2022 ). Moreover, the transendothelial electrical resistance (TEER), which is a non-invasive technique that measures the electrical impedance across the monolayer of endothelial cells (ECs) forming the BBB and its paracellular tightness, is continuously monitored ( Srinivasan and Kolli, 2019 ; Neuhaus, 2021 ; Jagtiani et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

“…In the same way, the cell viability and junction proteins expression can be evaluated by immunocytochemistry using light-phase/confocal imaging ( Jagtiani et al, 2022 ). Moreover, the transendothelial electrical resistance (TEER), which is a non-invasive technique that measures the electrical impedance across the monolayer of endothelial cells (ECs) forming the BBB and its paracellular tightness, is continuously monitored ( Srinivasan and Kolli, 2019 ; Neuhaus, 2021 ; Jagtiani et al, 2022 ). The transepithelial permeability and paracellular markers (e.g., dextran, mannose, sucrose, bovine serum albumin, immunoglobulin) are also evaluated ( Natarajan et al, 2017 ; Bhalerao et al, 2020 ; Williams-Medina et al, 2021 ), as well as the cellular metabolism as nutrients consumption and metabolites production ( Janigro et al, 2000 ; Cucullo et al, 2002 ), and the microenvironmental conditions (e.g., extracellular matrix (ECM), shear stress and cell sources) ( Bischel et al, 2016 ; Linville and Searson, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

On the quest of reliable 3D dynamic in vitro blood-brain barrier models using polymer hollow fiber membranes: Pitfalls, progress, and future perspectives

Mantecón-Oria

Rivero

Diban

et al. 2022

Front. Bioeng. Biotechnol.

View full text Add to dashboard Cite

With the increasing concern of neurodegenerative diseases, the development of new therapies and effective pharmaceuticals targeted to central nervous system (CNS) illnesses is crucial for ensuring social and economic sustainability in an ageing world. Unfortunately, many promising treatments at the initial stages of the pharmaceutical development process, that is at the in vitro screening stages, do not finally show the expected results at the clinical level due to their inability to cross the human blood-brain barrier (BBB), highlighting the inefficiency of in vitro BBB models to recapitulate the real functionality of the human BBB. In the last decades research has focused on the development of in vitro BBB models from basic 2D monolayer cultures to 3D cell co-cultures employing different system configurations. Particularly, the use of polymeric hollow fiber membranes (HFs) as scaffolds plays a key role in perfusing 3D dynamic in vitro BBB (DIV-BBB) models. Their incorporation into a perfusion bioreactor system may potentially enhance the vascularization and oxygenation of 3D cell cultures improving cell communication and the exchange of nutrients and metabolites through the microporous membranes. The quest for developing a benchmark 3D dynamic in vitro blood brain barrier model requires the critical assessment of the different aspects that limits the technology. This article will focus on identifying the advantages and main limitations of the HFs in terms of polymer materials, microscopic porous morphology, and other practical issues that play an important role to adequately mimic the physiological environment and recapitulate BBB architecture. Based on this study, we consider that future strategic advances of this technology to become fully implemented as a gold standard DIV-BBB model will require the exploration of novel polymers and/or composite materials, and the optimization of the morphology of the membranes towards thinner HFs (<50 μm) with higher porosities and surface pore sizes of 1–2 µm to facilitate the intercommunication via regulatory factors between the cell co-culture models of the BBB.

show abstract

Engineering Neurovascular Unit and Blood–Brain Barrier for Ischemic Stroke Modeling

Liu

Tang

Zhang

et al. 2023

Adv Healthcare Materials

View full text Add to dashboard Cite

Ischemic stroke is a primary vascular disease of the central nervous system characterized by high morbidity, mortality, and healthcare costs. As conventional ischemic stroke models fail to predict therapeutic efficacy, in vitro neurovascular unit (NVU)/blood–brain barrier (BBB) models are utilized to model ischemic stroke through replicating the cell–cell interactions and mimicking the blood flow and anatomical features of the brain. Here, an overview of transwell, microfluidic, and hydrogel‐based NVU/BBB models is provided, including cell types, engineering approaches, and the simulation of physiological and pathological features of NVU/BBB after ischemic stroke. Collectively, recent advances in 3D‐printed NVU models are emphasized, which are anticipated to be a promising system for more reliable mechanistic studies and preclinical drug screenings that can eventually accelerate the drug development process for the ischemic stroke therapy.

show abstract

In vitro blood brain barrier models: An overview

Cited by 46 publications

References 132 publications

Bisdemethoxycurcumin (BDC)-Loaded H-Ferritin-Nanocages Mediate the Regulation of Inflammation in Alzheimer’s Disease Patients

Bisdemethoxycurcumin (BDC)-Loaded H-Ferritin-Nanocages Mediate the Regulation of Inflammation in Alzheimer’s Disease Patients

On the quest of reliable 3D dynamic in vitro blood-brain barrier models using polymer hollow fiber membranes: Pitfalls, progress, and future perspectives

Engineering Neurovascular Unit and Blood–Brain Barrier for Ischemic Stroke Modeling

Contact Info

Product

Resources

About