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. 2021 Sep 23;9:696668. doi: 10.3389/fcell.2021.696668

TABLE 3.

Biomarkers and assays for nanotoxicity evaluation in 3D organoid models.

Organoid Markers Indication Analysis
Liver Cell viability, morphology, Albumin, Bile, Cytochrome 450, ALT, GGT and AST, Catalase and carbamoyl phosphate synthetase-1 isoforms, and proinflammatory cytokines Cytotoxicity, liver secretion, xenobiotic clearance, and oxidative stress MTT assay, electron microscopy, biochemical, and gene expression study
Kidney Apoptosis, morphology, Blood urea nitrogen (BUN), EPO, γ-glutamyltransferase production, SIX2, NPHS1, SAL1, WT1, PAX2, Bmp4, CITED1, KIM-1, trefoil factor 3 (TFF-3), beta-2 microglobulin, cystatin C, albumin, total protein, clusterin, neutrophil gelatinase-associated lipocalin, IL-18 and osteopontin, proinflammatory cytokines, and ROS generation Cell viability, Kidney function, secretion, development and regeneration test, and oxidative stress MTT assay, electron microscopy, biochemical, ELISA, and gene expression study
Heart Alpha-actin, CD45, CD31, LDH, troponin, and heart beat assay Cardiomyositis, contractile and ion channel function Biochemical, ELISA, gene expression study, and ECG
Brain Proinflammatory cytokines, ROS generation, CORIN, OTX2, MAP2, and TBR Oxidative stress, Brain developmental analysis Gene expression study, immunoassays
GIT CyP3A4,CYP450, Cyp2b10, Cyp3a11, ABCB1/MDR1, and XPGs including alcohol dehydrogenase Adh1, aldehyde dehydrogenase Aldh1a1, and Aldh1a7, secrete gastric intrinsic factor, pepsinogen C, and mucin GIT function test for detoxification, xenobiotic clearance and enzyme secretion Gene expression study and ELISA or biochemical assay
Lung KL6, MMP1&7, PFT ABG, and DLCO Lung function and structural integrity analysis Biochemical, ELISA, and gene expression study
Pancreas Insulin, amylase, lipase, LDH, PDX1, NKX6.1, Synaptophysin, and islet amyloid polypeptide Pancreas endocrine function, enzyme assay, and developmental assessment Biochemical, ELISA and gene expression study
Tumor M2-PK, Wnt Signaling pathways molecules, Her2, cytology, copy number alterations (CNAs), hematoxylin and eosin (H&E) staining, live dead cell, ATP measurement, and Annexin V-FITC/PI staining Tumor-specific test Gene expression study, Western blotting, immunohistochemistry, and microscopy
Testis Testosterone and inhibin B Function test ELISA, Western blotting, and immunohistochemistry
Dental epithelial organoids α-Amylase activity Function test ELISA, Western blotting, and immunohistochemistry