Human hepatoma cell lines on gas foaming templated alginate scaffolds for in vitro drug-drug interaction and metabolism studies

Stampella, Alessandra; Rizzitelli, G.; Donati, Francesco; Mazzarino, Monica; Torre, Xavier de la; Botrè, Francesco; Giardi, Maria Federica; Dentini, Mariella; Barbetta, Andrea; Massimi, Mara

doi:10.1016/j.tiv.2015.10.002

Cited by 8 publications

(2 citation statements)

References 30 publications

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“…In this study, an integrated microdevice mimicked the in vivo process of hepatic metabolism upon drug exposure. HepG2 cells representing the liver were cultured on the top layer of the chamber, due to this cell type could generate the required enzymes analogous to humans in the study of drug metabolism ( Matthieu et al, 2014 ; Yang et al, 2014 ; Stampella et al, 2015 ; Tang et al, 2015 ; Zhang et al, 2015 ; Cui et al, 2016 ). In the pre-experiment, the metabolic function of HepG2 cells satisfied the experimental purpose compared with other hepatocytes.…”

Section: Discussionmentioning

confidence: 99%

Analysis of metabolites and metabolism-mediated biological activity assessment of ginsenosides on microfluidic co-culture system

Sun

et al. 2023

Front. Pharmacol.

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In vivo, the complex process of drugs metabolism alters the change in drug composition and determines the final pharmacological properties of oral drugs. Ginsenosides are primary constituents of ginseng, whose pharmacological activities are greatly affected by liver metabolism. However, the predictive power of existing in vitro models is poor due to their inability to mimic the complexity of drug metabolism in vivo. The advance of organs-on-chip-based microfluidics system could provide a new in vitro drug screening platform by recapitulating the metabolic process and pharmacological activity of natural product. In this study, an improved microfluidic device was employed to establish an in vitro co-culture model by culturing multiple cell types in compartmentalized microchambers. Different cell lines were seeded on the device to examine the metabolites of ginsenosides from the hepatocytes in top layer and its resulting efficacy on the tumors in bottom layer. Metabolism dependent drug efficacy of Capecitabine in this system demonstrated the model is validated and controllable. High concentrations of CK, Rh2 (S), and Rg3 (S) ginsenosides showed significant inhibitory effects on two types of tumor cells. In addition, apoptosis detection showed that Rg3 (S) through liver metabolism promoted early apoptosis of tumor cells and displayed better anticancer activity than prodrug. The detected ginsenoside metabolites indicated that some protopanaxadiol saponins were converted into other anticancer aglycones in varying degrees due to orderly de-sugar and oxidation. Ginsenosides exhibited different efficacy on target cells by impacting their viabilities, indicating hepatic metabolism plays an important role in determining ginsenosides efficacy. In conclusion, this microfluidic co-culture system is simple, scalable, and possibly widely applicable in evaluating anticancer activity and metabolism of drug during the early developmental phases of natural product.

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Section: Discussionmentioning

confidence: 99%

Analysis of metabolites and metabolism-mediated biological activity assessment of ginsenosides on microfluidic co-culture system

Sun

et al. 2023

Front. Pharmacol.

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“…HepG2 cells representing the liver were cultured on the chamber of the top layer because this cell type could generate the required enzymes analogous to humans for the study of drug metabolism. 16,[32][33][34][35] To investigate the drug efficacy and selectivity of CAP on different organ-specific cells, the three cell lines MDA-MB-231 (breast cancer), A549 (lung cancer) and GES-1 (gastric normal cells) were seeded into the separated micro-chambers in the bottom layer (Fig. 2).…”

Section: Design Of Multilayer and Multi-functional Organs-on-a-chip D...mentioning

confidence: 99%

Assessment of metabolism-dependent drug efficacy and toxicity on a multilayer organs-on-a-chip

Guo

et al. 2016

Integr. Biol.

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Pharmaceutical development is greatly hindered by the poor predictive power of existing in vitro models for drug efficacy and toxicity testing. In this work, we present a new and multilayer organs-on-a-chip device that allows for the assessment of drug metabolism, and its resultant drug efficacy and cytotoxicity in different organ-specific cells simultaneously. Four cell lines representing the liver, tumor (breast cancer and lung cancer), and normal tissue (gastric cells) were cultured in the compartmentalized micro-chambers of the multilayer microdevice. We adopted the prodrug capecitabine (CAP) as a model drug. The intermediate metabolites 5'-deoxy-5-fluorocytidine (DFUR) of CAP that were metabolized from liver and its active metabolite 5-fluorouracil (5-FU) from the targeted cancer cells and normal tissue cells were identified using mass spectrometry. CAP exhibited strong cytoxicity on breast cancer and lung cancer cells, but not in normal gastric cells. Moreover, the drug-induced cytotoxicity on cells varied in various target tissues, suggesting the metabolism-dependent drug efficacy in different tissues as exisits in vivo. This in vitro model can not only allow for characterizing the dynamic metabolism of anti-cancer drugs in different tissues simultaneously, but also facilitate the assessment of drug bioactivity on various target tissues in a simple way, indicating the utility of this organs-on-chip for applications in pharmacodynamics/pharmacokinetics studies, drug efficacy and toxicity testing.

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Gas foaming technologies for 3D scaffold engineering

Costantini

Barbetta

2018

Functional 3D Tissue Engineering Scaffolds

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Human hepatoma cell lines on gas foaming templated alginate scaffolds for in vitro drug-drug interaction and metabolism studies

Cited by 8 publications

References 30 publications

Analysis of metabolites and metabolism-mediated biological activity assessment of ginsenosides on microfluidic co-culture system

Analysis of metabolites and metabolism-mediated biological activity assessment of ginsenosides on microfluidic co-culture system

Assessment of metabolism-dependent drug efficacy and toxicity on a multilayer organs-on-a-chip

Gas foaming technologies for 3D scaffold engineering

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