Table 1.
Examples of multi-organ microdevices and their demonstrated capabilities for drug testing applications
| Organ combination | Tested Drug/Toxin | Demonstrated capability | Endpoints | References |
|---|---|---|---|---|
| GI-tract-liver | Acetaminophen, 7-ethoxycoumarin (7-EC), 7-hydroxycoumar in (7-HC) and lidocaine | Metabolism of acetaminophen in the GI-tract and liver, modulated acetaminophen toxicity in the liver due to the presence of the GI-tract, Modulation of liver toxicity due to addition of bile acids to GI-tract model | Acetaminophe n metabolite detection via HPLC, live/dead assay, P450 7A1 (CYP7A1) activity in the liver | (Mahler, Esch, Glahn, & Shuler, 2009a; van Midwoud, Merema, Verpoorte, & Groothuis, 2010) |
| Microvasculature-liver | Not challenged with any drugs | Increased albumin and urea production as a result of co-culture | Consumption of glucose by liver cells, albumin synthesis, urea production | (Chang et al., 2012; Guzzardi. Vozzi, & Ahluwalia, 2009; P. J. Lee et al., 2007: Vozzi, Heinrich, Bader, & Ahluwalia, 2008) |
| Liver-tumor-bone marrow | tegafur | Pro-drug conversion, synergy of anti-cancer drugs | Live/dead assay | (Sung & Shuler, 2009a) |
| Liver-lung-fat | naphthalene | Identification of toxic metabolite, modulation of toxicity by fat tissue | Live/dead assay | (Viravaidya & Shuler, 2004a; Viravaidya, Sin, & Shuler, 2004a) |
| Liver-kidney | ifosfamide | Pro-drug conversion and nephrotoxicity | Metabolite detection via mass spectrometry, cell proliferation, calcium release | (Choucha-Snouber et al., 2012) |
| Liver-lung-kidney-fat | TGF-β1 | Dose-dependent response of each cell type to TGF-β1 and tissue-specific support through localization of TGF-β1 release | Albumin secretion, PROD activity, GGT activity, adiponectin secretion | (C. Zhang, Zhao, Abdul Rahim, van Noort, & Yu, 2009b) |
| Skin-liver | bpV(phen) | Uptake of bpV(phen) through the skin and subsequent stimulation of glucose consumption | Glucose consumption | (Brand et al., 2000) |