TABLE 7

Overview of multiorgan-on-a-chip combinations used for pharmacological or toxicological applications

ApplicationTissuesType of CultureType of CellsFindingsReferences
ToxicityLiver and heart3DiPSC-derivedMetabolic interaction underlying clomipramine toxicity(Yin et al., 2021)
ToxicityLiver and heart2D and 3DiPSC-derived and primary cellsMetabolic interaction underlying cyclophosphamide and terfenadine toxicity(Oleaga et al., 2018)
ToxicityLiver and heart3DiPSC-derived and primary cellsTissue-specific toxicity of acetaminophen and doxorubicin(Zhang et al., 2017)
ToxicityLiver and kidney2DCell lines and primary cellsMetabolic interaction underlying ifosfamide and verapamil nephrotoxicity(Li et al., 2018c)
ToxicityLiver and kidney2DCell linesTissue interactions in vitamin D3 bioactivation(Theobald et al., 2019)
ToxicityLiver and lung3D and ALICell linesLiver cells reduce aflatoxin B1 pulmonary toxicity(Bovard et al., 2018)
ToxicityLiver and lung3D and ALICell linesLiver cells reduce aflatoxin B1 pulmonary toxicity(Schimek et al., 2020)
ToxicityLiver, heart, and lung3DiPSC-derived and primary cellsLung is essential in bleomycin-induced cardiotoxicity(Skardal et al., 2017)
ToxicityLiver, heart, lung, endothelium, brain, and testes3DiPSC-derived, cell lines, and primary cellsMetabolic interaction underlying ifosfamide neurotoxicity(Rajan et al., 2020)
ToxicityLiver, brain, pancreas, lung, heart, gut, and endometrium2DCell lines and primary cellsTolcapone metabolism and mechanism of action(Wang et al., 2019b)
ToxicityLiver, cancer, bone marrow3DCell linesHepatic bioactivation of capecitabine and tegafur(LaValley et al., 2021)
ToxicityLiver and cancer2DCell linesHepatic bioactivation of capecitabine and tegafur(Satoh et al., 2017)
ToxicityLiver and cancer2D and 3DCell linesHepatic bioactivation and inactivation of ifosfamide and temozolomide, respectively(Ma et al., 2012)
ToxicityLiver and cancer2DCell linesEffects of hepatic metabolism on luteolin toxicity(Lee et al., 2017b)
ToxicityLiver and cancer2DCell linesHepatic bioactivation of irinotecan(Shinha et al., 2020)
ToxicityLiver, intestine, and lung2DCell linesHepatic bioactivation of cyclophosphamide or irinotecan(Kimura et al., 2015)
ToxicityLiver, lung, kidney, and adipose tissue3DCell linesTissue-specific effects of TGFβ(Zhang et al., 2009)
ToxicityLiver, heart, lung, endothelium, testis, colon, and brain3DPrimary stem cells and primary cellsComparison of tissue-specific toxicity in coculture(Skardal et al., 2020)
PKLiver and intestine3DCell lines and primary cellsSystem retains drug absorption of panadol, mannitol, and caffeine(Chen et al., 2018)
PKLiver and intestine2D and 3DCell lines and primary cellsSystem retains drug permeability similar to monoculture(Esch et al., 2016)
PKLiver and intestine2DCell linesApigenin mertabolism in both intestine and liver(Choe et al., 2017)
PKLiver and intestine3DCell lines and primary cellsEstimation of diclofenac and hydrocortisone permeability and clearance(Tsamandouras et al., 2017)
PKLiver and intestine2DCell linesAbsorption of fatty acid and evaluation of antisteatotic effect of metformin and XL-335(Jeon et al., 2021)
Gut-brain-axisBrain and intestine2DiPSC-derivedEvaluation of the impact of the intestinal microflora on neurodegeneration(Raimondi et al., 2019)
Gut-brain-axisLiver, intestine, and brain2D and 3DPrimary stem cells, cell lines, and primary cellsMicrobiome-derived short-chain fatty acids increase the expression of pathology-associated pathways in neurodegenerative disease(Trapecar et al., 2021)
Metastasis formationBrain and lung2DCell linesNSCLC metastasizing propensity to brain(Liu et al., 2019)
Glucose metabolismLiver and pancreas3DCell lines and primary cellsRecapitulation of glucose metabolism and homeostasis(Bauer et al., 2017)
Glucose metabolismLiver, pancreas, and skeletal muscle2DCell linesRecapitulation of glucose metabolism and homeostasis(Lee et al., 2019)

  • ALI, air-liquid interface; NSCLC, non–small cell lung cancer; PK, pharmacokinetics.