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Comparison of Blood-Brain Barrier Models for in vitro Biological Analysis: One Cell Type vs Three Cell Types.

ABSTRACT: Different types of in vitro blood-brain barrier (BBB) models have been constructed and applied for drug transport to evaluate the efficacy of nano-carrier based drug delivery. However, the effectiveness of different types of BBB models has not been reported. In this paper, we developed two types of in vitro models: one-cell type BBB model developed using only endothelial cells and three-cell type BBB model obtained by co-culturing endothelial, pericyte and astrocyte cells. The nanoparticle transport mechanisms through BBB and transport efficiencies of the Lactoferrin attached silica nanoparticles were studied using both types of the in vitro BBB models. Compared with one-cell type model, the PSi-Lf NPs exhibit relatively lower transport efficiency across three-cell type BBB system. Moreover, the effects of the nanoparticle size on the transport efficacies are consistent for both models. For both types of BBB models, the transport efficacies of the NPs are size dependent, and the highest efficacies are achieved for NPs with 25 nm in diameter. Our experimental results indicate that the one-cell type and three-cell type BBB models are equivalent for evaluating and optimizing nanoparticle transport across BBB.

SUBMITTER: Song Y

PROVIDER: S-EPMC6980243 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Comparison of Blood-Brain Barrier Models for in vitro Biological Analysis: One Cell Type vs Three Cell Types.

Song Yang Y Cai Xiaoli X Du Dan D Dutta Prashanta P Lin Yuehe Y

ACS applied bio materials 20190125 3

Different types of in vitro blood-brain barrier (BBB) models have been constructed and applied for drug transport to evaluate the efficacy of nano-carrier based drug delivery. However, the effectiveness of different types of BBB models has not been reported. In this paper, we developed two types of in vitro models: one-cell type BBB model developed using only endothelial cells and three-cell type BBB model obtained by co-culturing endothelial, pericyte and astrocyte cells. The nano ...[more]

PMID: 31984375

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Project description:Objectives: Improvements in human stem cell-derived cardiomyocyte (hSC-CM) technology have promoted their use for drug testing and disease investigations. Several in silico hSC-CM models have been proposed to augment interpretation of experimental findings through simulations. This work aims to assess the response of three hSC-CM in silico models (Koivumäki2018, Kernik2019, and Paci2020) to simulated drug action, and compare simulation results against in vitro data for 15 drugs. Methods: First, simulations were conducted considering 15 drugs, using a simple pore-block model and experimental data for seven ion channels. Similarities and differences were analyzed in the in silico responses of the three models to drugs, in terms of Ca2+ transient duration (CTD90) and occurrence of arrhythmic events. Then, the sensitivity of each model to different degrees of blockage of Na+ (INa), L-type Ca2+ (ICaL), and rapid delayed rectifying K+ (IKr) currents was quantified. Finally, we compared the drug-induced effects on CTD90 against the corresponding in vitro experiments. Results: The observed CTD90 changes were overall consistent among the in silico models, all three showing changes of smaller magnitudes compared to the ones measured in vitro. For example, sparfloxacin 10 µM induced +42% CTD90 prolongation in vitro, and +17% (Koivumäki2018), +6% (Kernik2019), and +9% (Paci2020) in silico. Different arrhythmic events were observed following drug application, mainly for drugs affecting IKr. Paci2020 and Kernik2019 showed only repolarization failure, while Koivumäki2018 also displayed early and delayed afterdepolarizations. The spontaneous activity was suppressed by Na+ blockers and by drugs with similar effects on ICaL and IKr in Koivumäki2018 and Paci2020, while only by strong ICaL blockers, e.g. nisoldipine, in Kernik2019. These results were confirmed by the sensitivity analysis. Conclusion: To conclude, The CTD90 changes observed in silico are qualitatively consistent with our in vitro data, although our simulations show differences in drug responses across the hSC-CM models, which could stem from variability in the experimental data used in their construction.

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Comparison of Blood-Brain Barrier Models for in vitro Biological Analysis: One Cell Type vs Three Cell Types.

Publications

Comparison of Blood-Brain Barrier Models for <i>in vitro</i> Biological Analysis: One Cell Type vs Three Cell Types.

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