A Human Ovarian Tumor & Liver Organ-on-Chip for Simultaneous and More Predictive Toxo-Efficacy Assays
In oncology, the poor success rate of clinical trials is becoming increasingly evident due to the weak predictability of preclinical assays, which either do not recapitulate the complexity of human tissues (i.e., in vitro tests) or reveal species-specific outcomes (i.e., animal testing). Therefore,...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-02-01
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| Series: | Bioengineering |
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| Online Access: | https://www.mdpi.com/2306-5354/10/2/270 |
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| author | Arianna Fedi Chiara Vitale Marco Fato Silvia Scaglione |
| author_facet | Arianna Fedi Chiara Vitale Marco Fato Silvia Scaglione |
| author_sort | Arianna Fedi |
| collection | DOAJ |
| description | In oncology, the poor success rate of clinical trials is becoming increasingly evident due to the weak predictability of preclinical assays, which either do not recapitulate the complexity of human tissues (i.e., in vitro tests) or reveal species-specific outcomes (i.e., animal testing). Therefore, the development of novel approaches is fundamental for better evaluating novel anti-cancer treatments. Here, a multicompartmental organ-on-chip (OOC) platform was adopted to fluidically connect 3D ovarian cancer tissues to hepatic cellular models and resemble the systemic cisplatin administration for contemporarily investigating drug efficacy and hepatotoxic effects in a physiological context. Computational fluid dynamics was performed to impose capillary-like blood flows and predict cisplatin diffusion. After a cisplatin concentration screening using 2D/3D tissue models, cytotoxicity assays were conducted in the multicompartmental OOC and compared with static co-cultures and dynamic single-organ models. A linear decay of SKOV-3 ovarian cancer and HepG2 liver cell viability was observed with increasing cisplatin concentration. Furthermore, 3D ovarian cancer models showed higher drug resistance than the 2D model in static conditions. Most importantly, when compared to clinical therapy, the experimental approach combining 3D culture, fluid-dynamic conditions, and multi-organ connection displayed the most predictive toxicity and efficacy results, demonstrating that OOC-based approaches are reliable 3Rs alternatives in preclinic. |
| first_indexed | 2024-03-11T09:07:37Z |
| format | Article |
| id | doaj.art-01034a6870f44ec288854cae28cfb7c3 |
| institution | Directory Open Access Journal |
| issn | 2306-5354 |
| language | English |
| last_indexed | 2024-03-11T09:07:37Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Bioengineering |
| spelling | doaj.art-01034a6870f44ec288854cae28cfb7c32023-11-16T19:12:04ZengMDPI AGBioengineering2306-53542023-02-0110227010.3390/bioengineering10020270A Human Ovarian Tumor & Liver Organ-on-Chip for Simultaneous and More Predictive Toxo-Efficacy AssaysArianna Fedi0Chiara Vitale1Marco Fato2Silvia Scaglione3Department of Computer Science, Bioengineering, Robotics and Systems Engineering (DIBRIS), University of Genoa, 16126 Genoa, ItalyNational Research Council of Italy, Institute of Electronic, Computer and Telecommunications (IEIIT), 16149 Genoa, ItalyDepartment of Computer Science, Bioengineering, Robotics and Systems Engineering (DIBRIS), University of Genoa, 16126 Genoa, ItalyNational Research Council of Italy, Institute of Electronic, Computer and Telecommunications (IEIIT), 16149 Genoa, ItalyIn oncology, the poor success rate of clinical trials is becoming increasingly evident due to the weak predictability of preclinical assays, which either do not recapitulate the complexity of human tissues (i.e., in vitro tests) or reveal species-specific outcomes (i.e., animal testing). Therefore, the development of novel approaches is fundamental for better evaluating novel anti-cancer treatments. Here, a multicompartmental organ-on-chip (OOC) platform was adopted to fluidically connect 3D ovarian cancer tissues to hepatic cellular models and resemble the systemic cisplatin administration for contemporarily investigating drug efficacy and hepatotoxic effects in a physiological context. Computational fluid dynamics was performed to impose capillary-like blood flows and predict cisplatin diffusion. After a cisplatin concentration screening using 2D/3D tissue models, cytotoxicity assays were conducted in the multicompartmental OOC and compared with static co-cultures and dynamic single-organ models. A linear decay of SKOV-3 ovarian cancer and HepG2 liver cell viability was observed with increasing cisplatin concentration. Furthermore, 3D ovarian cancer models showed higher drug resistance than the 2D model in static conditions. Most importantly, when compared to clinical therapy, the experimental approach combining 3D culture, fluid-dynamic conditions, and multi-organ connection displayed the most predictive toxicity and efficacy results, demonstrating that OOC-based approaches are reliable 3Rs alternatives in preclinic.https://www.mdpi.com/2306-5354/10/2/2703D in vitro modelsmulti-organdrug efficacyfluid-dynamicsorgan-on-chipovarian cancer |
| spellingShingle | Arianna Fedi Chiara Vitale Marco Fato Silvia Scaglione A Human Ovarian Tumor & Liver Organ-on-Chip for Simultaneous and More Predictive Toxo-Efficacy Assays Bioengineering 3D in vitro models multi-organ drug efficacy fluid-dynamics organ-on-chip ovarian cancer |
| title | A Human Ovarian Tumor & Liver Organ-on-Chip for Simultaneous and More Predictive Toxo-Efficacy Assays |
| title_full | A Human Ovarian Tumor & Liver Organ-on-Chip for Simultaneous and More Predictive Toxo-Efficacy Assays |
| title_fullStr | A Human Ovarian Tumor & Liver Organ-on-Chip for Simultaneous and More Predictive Toxo-Efficacy Assays |
| title_full_unstemmed | A Human Ovarian Tumor & Liver Organ-on-Chip for Simultaneous and More Predictive Toxo-Efficacy Assays |
| title_short | A Human Ovarian Tumor & Liver Organ-on-Chip for Simultaneous and More Predictive Toxo-Efficacy Assays |
| title_sort | human ovarian tumor liver organ on chip for simultaneous and more predictive toxo efficacy assays |
| topic | 3D in vitro models multi-organ drug efficacy fluid-dynamics organ-on-chip ovarian cancer |
| url | https://www.mdpi.com/2306-5354/10/2/270 |
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