Nephrotoxicity Evaluation by Kidney-on-a-chip Model

Kidney-on-a-chip model involves the construction of cell models in micro-engineered systems, with the principal strengths of inducing cell-associated physiological properties, including cell morphology and dimensionality, generating fluid shear stresses, and mechanical strains, and providing a cellular co-culture environment. Creative Biolabs offers the service of evaluating the nephrotoxicity of agents in the kidney-on-a-chip model to support the screening of candidates.

Features of Kidney-on-a-chip Model

• Composed of qualified human primary proximal tubular epithelial cells and human primary renal microvascular endothelial cells isolated from glomeruli, simulating the interactions at the proximal tubular-vascular interface, which is separated by matrix protein-containing micropore membranes.
• Exhibit a realistic hyperdifferentiated renal-like phenotype and maintains the expression and localization of functional proteins.
• Simulate the mechanism of drug-induced nephrotoxicity, changes in renal metabolism, and expression of relevant markers.
• Maintain stable albumin reabsorption function and characteristic morphology for ~14 days.

Advantages of Kidney-on-a-chip Model

• The model consists of key renal cell populations and is exposed to a fluid culture environment, reconstructing the dynamic renal microenvironment.
• 3D modeling maintains the excellent polarity and cilia formation of epithelial cells, avoiding the possibility of cellular loss of differentiation in monoculture models.
• The model retains the high expression and sensitivity of renal transporter proteins, ensuring a concentration-dependent timely reaction to the tested agent.
• Avoiding the interferences to the evaluation caused by the use of species-differentiated animal models and immortalized cellular models.

Nephrotoxicity Evaluation by the Kidney-on-a-chip Model

The kidney-on-a-chip model supports the evaluation of nephrotoxicity in healthy renal landscapes and drug-treated models based on multiple evaluation indicators assays, including but not limited to,

Identifying Cell Structure and Function

• Dome forming in renal tubular epithelial cells reflects the function of the cell in transporting water and ions.
• Measurement of transmembrane resistance reflects the degree of cellular tight junctions and barrier function.
• Identification of the transporter protein expression, including transfer-in proteins solute carrier family and transfer-out proteins such as multidrug resistance proteins.

Cell injury-related indicators

• Cell Viability
• Cell Membrane Integrity
• Cell metabolism
• Apoptosis or necrosis

Specific nephrotoxicity markers

• KIM-1 (kidney injury molecule-1)
• Clusterin
• uTP (Urinary total protein)
• β2-MG (β2-microglobulin)
• Albumin
• Trefoil factor-3
• etc.

Fig. 1 Types of bioengineered kidney models.¹

Creative Biolabs has accumulated insights into the imitated kidney-on-a-chip model to precisely predict the toxic effects of possible medications on the kidney. Please contact us to learn more about the evaluation process and to experience the evaluation power of the model.

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