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. Author manuscript; available in PMC: 2025 Jun 20.
Published in final edited form as: Circ Res. 2025 May 22;136(11):1476–1493. doi: 10.1161/CIRCRESAHA.125.325497

Table 2.

Benchmarking Parameters for Heart-on-a-Chip, Liver-on-a-Chip, Kidney-on-a-Chip, and Adipose-on-a-Chip Organ Models

Model Benchmarking parameters
Heart-on-a-chip Elongated, rod-like cardiomyocytes149
Expression of adult ventricular genes (MYH7, MYL2, and TNNI3)149
Contractile stress 30–60 mN/mm3,150,151
Positive force-frequency ratio, characteristic notch at the top of upstroke152
RMP −90 mV, action potential amplitude 100–110 mV, action potential duration 230–300 ms152
Depolarization velocity 250–300 V/s, conduction velocity 30–100 cm/s152
Well-developed sarcoplasmic reticulum structure and function, gene expression of calcium-handling machinery149
Cytosolic calcium concentration 1 μm during systole, 100 nmol/L during diastole153
Reliance on fatty acid oxidation (>70%)154
Liver-on-a-chip Albumin production >37 μg per day/1 million hepatocytes155
Urea synthesis >56 μg per day/1 million hepatocytes155
Expression of phase I and II CYP450 enzymes, hepatocyte uptake, and efflux transports155
Polygonal, nonrounded, polarized hepatocytes155
Presence of bile canaliculi (BSEP, MRP2, and AQP1) and bile acid synthesis155
Presence of Kupffer cells (CD68) and stellate cells (desmin)155
Kidney-on-a-chip Albumin reabsorption efficiency of at least 80%156
Glucose reabsorption efficiency of at least 95%157
Transepithelial electrical resistance 6–10 Ω·cm2 (proximal tubule),158 100–500 Ω·cm2 (renal cell lines)159
Expression of podocyte markers (NPSH1, NPSH2, and WT1)160
Expression of mesangial cell markers (GATA3, PDGFRA, and ITGA8)160
Expression of glomerular endothelial cell markers (EHD3, EMCN, KDR, and CD31)160
Brush border enzyme activity: Na+/K+-ATPase, alkaline phosphatase, γ-glutamyltransferase160
Adipose-on-a-chip Adipocytes >55 μm in diameter161
Unilocular lipid contents, expression of maturation markers (PPARG, FABP4, and adiponectin)162
Evidence of insulin-stimulated glucose uptake162
Evidence of lipid metabolism (free fatty acid uptake, glycerol release)162
Incorporation of resident immune cells (CD68) and stromovascular cells (CD31, ACTA2)162

Parameters are reflective of values normally observed for mature cardiomyocytes, hepatocytes, proximal tubule epithelial cells/glomerular cells, and adipocytes. ACTA2 indicates alpha-smooth muscle actin; AQP1 indicates aquaporin 1; BSEP, bile salt export pump; CD, cluster of differentiation; CYP450, cytochrome P450; DES, desmin; EHD3, EH domain containing 3; EMCN, endomucin; FABP4, fatty acid-binding protein 4; GATA3, GATA-binding protein 3; ITGA8, integrin alpha 8; KDR, Kinase Insert Domain Receptor; MRP2, multidrug resistance-associated protein 2; MYH7, myosin heavy chain 7; MYL2, myosin light chain 2; NPSH1, nephrin; NPSH2, podocin; PDGFRA, platelet-derived growth factor receptor alpha; PPARG, peroxisome proliferator-activated receptor gamma; RMP, resting membrane potential; TNNI3, troponin I type 3; WT1, Wilms tumor-1; and WT, wild-type.