The DOI matches its Crossref record; 13 of the 13 references it cites were found in a registry or an index.
A 3D microfluidic liver model for high throughput compound toxicity screening in the OrganoPlate®
Open accessAbstract
We report the development, automation and validation of a 3D, microfluidic liver-on-a-chip for high throughput hepatotoxicity screening, the OrganoPlate LiverTox™. The model is comprised of aggregates of induced pluripotent stem cell (iPSC)-derived hepatocytes (iHep) seeded in an extracellular matrix in the organ channel and co-cultured with endothelial cells and THP-1 monoblasts differentiated to macrophages seeded in the vascular channel of the 96 well Mimetas OrganoPlate 2-lane. A key component of high throughput screening is automation and we report a protocol to seed, dose, collect and replenish media and add assay reagents in the OrganoPlate 2-lane using a standard laboratory liquid handling robot. A combination of secretome measurements and image-based analysis was used to demonstrate stable 15 day cell viability, albumin and urea secretion. Over the same time-period, CYP3A4 activity increased and alpha-fetoprotein secretion decreased suggesting further maturation of the iHeps. Troglitazone, a clinical hepatotoxin, was chosen as a control compound for validation studies. Albumin, urea, hepatocyte nuclear size and viability staining provided Robust Z’factors > 0.2 in plates treated 72 h with 180 μM troglitazone compared with a vehicle control. The viability assay provided the most robust statistic for a Robust Z’ factor = 0.6. A small library of 159 compounds with known liver effects was added to the OrganoPlate LiverTox model for 72 h at 50 μM and the Toxicological Prioritization scores were calculated. A follow up dose-response evaluation of select hits revealed the albumin assay to be the most sensitive in calculating TC50 values. This platform provides a robust, novel model which can be used for high throughput hepatotoxicity screening.
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Human organs-on-chips for disease modelling, drug development and personalized medicine
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3d organ-on-a-chip: the convergence of microphysiological systems and organoids
Baptista, L. S., Porrini, C., Kronemberger, G. S., Kelly, D. J., & Perrault, C. M. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.1043117 · Cited by 90
“In general, the process is not automated, with few exceptions (Bircsak et al., 2021).”
BackgroundMethodInfluential
Metadata
- Authors
- Bircsak, K. M., DeBiasio, R., Miedel, M., Alsebahi, A., Reddinger, R., Saleh, A., Shun, T., Vernetti, L. A., & Gough, A.
- Venue
- Toxicology
- Publisher
- Elsevier BV
- Published
- 2021-02
- Volume
- 450
- Pages
- 152667
- ISSN
- 0300-483X (ISSN-L)
- OpenAlex
- W3115778807
- Cited by
- 192
- References
- 13
- FWCI
- 8.54
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Bircsak, K. M., DeBiasio, R., Miedel, M., Alsebahi, A., Reddinger, R., Saleh, A., Shun, T., Vernetti, L. A., & Gough, A. (2021). A 3D microfluidic liver model for high throughput compound toxicity screening in the OrganoPlate®. Toxicology. https://doi.org/10.1016/j.tox.2020.152667
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