Matches in SemOpenAlex for { <https://semopenalex.org/work/W4387642743> ?p ?o ?g. }
- W4387642743 endingPage "1195" @default.
- W4387642743 startingPage "1195" @default.
- W4387642743 abstract "The liver is one of the key organs for exogenous and endogenous metabolism and is often a target for drug- and chemical-driven toxicity. A wide range of experimental approaches has been established to model and characterize the mechanisms of drug- and chemical-induced hepatotoxicity. A number of microfluidics-enabled in vitro models of the liver have been developed, but the unclear translatability of these platforms has hindered their adoption by the pharmaceutical industry; to achieve wide use for drug and chemical safety evaluation, demonstration of reproducibility and robustness under various contexts of use is required. One of these commercially available platforms is the PhysioMimix LC12, a microfluidic device where cells are seeded into a 3D scaffold that is continuously perfused with recirculating cell culture media to mimic liver sinusoids. Previous studies demonstrated this model’s functionality and potential applicability to preclinical drug development. However, to gain confidence in PhysioMimix LC12’s robustness and reproducibility, supplementary characterization steps are needed, including the assessment of various human hepatocyte sources, contribution of non-parenchymal cells (NPCs), and comparison to other models. In this study, we performed replicate studies averaging 14 days with either primary human hepatocytes (PHHs) or induced pluripotent stem cell (iPSC)-derived hepatocytes, with and without NPCs. Albumin and urea secretion, lactate dehydrogenase, CYP3A4 activity, and metabolism were evaluated to assess basal function and metabolic capacity. Model performance was characterized by different cell combinations under intra- and inter-experimental replication and compared to multi-well plates and other liver platforms. PhysioMimix LC12 demonstrated the highest metabolic function with PHHs, with or without THP-1 or Kupffer cells, for up to 10–14 days. iPSC-derived hepatocytes and PHHs co-cultured with additional NPCs demonstrated sub-optimal performance. Power analyses based on replicate experiments and different contexts of use will inform future study designs due to the limited throughput and high cell demand. Overall, this study describes a workflow for independent testing of a complex microphysiological system for specific contexts of use, which may increase end-user adoption in drug development." @default.
- W4387642743 created "2023-10-15" @default.
- W4387642743 creator A5019868317 @default.
- W4387642743 creator A5026711791 @default.
- W4387642743 creator A5027397488 @default.
- W4387642743 creator A5031835742 @default.
- W4387642743 creator A5043382534 @default.
- W4387642743 creator A5043889674 @default.
- W4387642743 creator A5055889724 @default.
- W4387642743 creator A5056717942 @default.
- W4387642743 creator A5067381195 @default.
- W4387642743 creator A5081575618 @default.
- W4387642743 creator A5090496194 @default.
- W4387642743 creator A5091169696 @default.
- W4387642743 date "2023-10-14" @default.
- W4387642743 modified "2023-10-15" @default.
- W4387642743 title "Reproducibility and Robustness of a Liver Microphysiological System PhysioMimix LC12 under Varying Culture Conditions and Cell Type Combinations" @default.
- W4387642743 cites W1699304230 @default.
- W4387642743 cites W1797606584 @default.
- W4387642743 cites W1821122251 @default.
- W4387642743 cites W1881590244 @default.
- W4387642743 cites W2004875910 @default.
- W4387642743 cites W2028278455 @default.
- W4387642743 cites W2082356514 @default.
- W4387642743 cites W2089436224 @default.
- W4387642743 cites W2111288662 @default.
- W4387642743 cites W2127676159 @default.
- W4387642743 cites W2130837075 @default.
- W4387642743 cites W2134520937 @default.
- W4387642743 cites W2159632264 @default.
- W4387642743 cites W2161364794 @default.
- W4387642743 cites W2335972659 @default.
- W4387642743 cites W2389381768 @default.
- W4387642743 cites W2413406085 @default.
- W4387642743 cites W2461581138 @default.
- W4387642743 cites W2473248288 @default.
- W4387642743 cites W2536520632 @default.
- W4387642743 cites W2537337063 @default.
- W4387642743 cites W2606463168 @default.
- W4387642743 cites W2608513314 @default.
- W4387642743 cites W2756261101 @default.
- W4387642743 cites W2791607331 @default.
- W4387642743 cites W2922901737 @default.
- W4387642743 cites W2948117622 @default.
- W4387642743 cites W2951694809 @default.
- W4387642743 cites W2990102938 @default.
- W4387642743 cites W3005321388 @default.
- W4387642743 cites W3008653267 @default.
- W4387642743 cites W3013934100 @default.
- W4387642743 cites W3017834715 @default.
- W4387642743 cites W3039565038 @default.
- W4387642743 cites W3084374992 @default.
- W4387642743 cites W3098314637 @default.
- W4387642743 cites W3113138899 @default.
- W4387642743 cites W3115203926 @default.
- W4387642743 cites W3115778807 @default.
- W4387642743 cites W3159479208 @default.
- W4387642743 cites W3163565378 @default.
- W4387642743 cites W3168883493 @default.
- W4387642743 cites W3179241489 @default.
- W4387642743 cites W3187749979 @default.
- W4387642743 cites W3201535006 @default.
- W4387642743 cites W4207037817 @default.
- W4387642743 cites W4220652963 @default.
- W4387642743 cites W4282914496 @default.
- W4387642743 cites W4285413549 @default.
- W4387642743 cites W4294553476 @default.
- W4387642743 cites W4295185250 @default.
- W4387642743 cites W4298003544 @default.
- W4387642743 cites W4310952187 @default.
- W4387642743 cites W4319225952 @default.
- W4387642743 cites W4319826836 @default.
- W4387642743 doi "https://doi.org/10.3390/bioengineering10101195" @default.
- W4387642743 hasPublicationYear "2023" @default.
- W4387642743 type Work @default.
- W4387642743 citedByCount "0" @default.
- W4387642743 crossrefType "journal-article" @default.
- W4387642743 hasAuthorship W4387642743A5019868317 @default.
- W4387642743 hasAuthorship W4387642743A5026711791 @default.
- W4387642743 hasAuthorship W4387642743A5027397488 @default.
- W4387642743 hasAuthorship W4387642743A5031835742 @default.
- W4387642743 hasAuthorship W4387642743A5043382534 @default.
- W4387642743 hasAuthorship W4387642743A5043889674 @default.
- W4387642743 hasAuthorship W4387642743A5055889724 @default.
- W4387642743 hasAuthorship W4387642743A5056717942 @default.
- W4387642743 hasAuthorship W4387642743A5067381195 @default.
- W4387642743 hasAuthorship W4387642743A5081575618 @default.
- W4387642743 hasAuthorship W4387642743A5090496194 @default.
- W4387642743 hasAuthorship W4387642743A5091169696 @default.
- W4387642743 hasBestOaLocation W43876427431 @default.
- W4387642743 hasConcept C104317684 @default.
- W4387642743 hasConcept C107459253 @default.
- W4387642743 hasConcept C145103041 @default.
- W4387642743 hasConcept C202751555 @default.
- W4387642743 hasConcept C2776200302 @default.
- W4387642743 hasConcept C2780035454 @default.
- W4387642743 hasConcept C55493867 @default.
- W4387642743 hasConcept C63479239 @default.