Kidney-On-A-Chip
The kidney is a vital organ in the human body. Simulating the kidney in vitro has very important theoretical and practical significance for the promotion of treatments such as hemodialysis and the evaluation of in vitro nephrotoxicity of new drugs. In the field of kidneys, organ chips are mainly used to build in vitro models to study the pathogenesis of the renal disease. In addition, in new drug clinical trials, the renal chip is regarded as a good in vitro model because of its high simulation, which has become a research hotspot in the field of new drug research and development.
Experimental Method of Kidney-on-a-Chip
- Prepare Microfluidic Chip
The fabrication of microfluidic chips requires the use of micro-nano processing technology to fabricate structures such as micropipes and micropores on the chip surface. The prepared chip needs surface treatment so that renal tubular cells can adhere and grow.
- Renal Tubular Cells were Cultured
Renal tubular cells were isolated from animal or human kidney tissues and cultured in Petri dishes until they reached a certain density and growth state.
- Assemble Microfluidic Chips
The cultured renal tubular cells were injected into the microfluidic chip and connected to the inlet and outlet pipes of the chip.
- Fluid Experiment
The pump system is used to inject the fluid of simulated urine into the microfluidic chip and control parameters such as flow velocity and pressure in the chip. In the experiment, different renal physiological states can be simulated by adjusting fluid composition and flow conditions, such as glomerular filtration, renal tubular reabsorption, and excretion.
- Data Acquisition and Analysis
Parameters such as renal tubular cells and fluid flow can be monitored and recorded in real-time by means of microscope and image processing system. At the same time, the metabolites, ion concentration, and drug metabolism of renal tubular cells under different flow conditions can also be analyzed.
Applications of Kidney-on-Chips
- Renal Tubule Chip
The renal tubule chip is composed of blood polar mass, urine polar mass and porous membrane between them. Most of the polar blocks are made of polydimethylsiloxane (PDMS). Vascular endothelial cells and renal tubular epithelial cells are planted on both sides of the porous membrane. The fluid in the blood polar mass flows through the vascular endothelial cells, and the liquid in the urine polar mass flows through renal tubular epithelial cells. The components in the two pathways are exchanged through the porous membrane, which can effectively simulate the function of renal tubules.
- Evaluation of Drug Nephrotoxicity
The proximal tubule is not only the main site of drug clearance, but also the main target of drug nephrotoxicity. Due to the limitations of animal experiments, drug nephrotoxicity is often found in late clinical trials. Because the renal tubule chip can more accurately and timely evaluate the degree of renal tubular damage, it can be used for drug screening and pharmacokinetic studies.
- Simulated Renal Fibrosis
The formation mechanism of renal fibrosis is still inconclusive. Studies have shown that epithelial-mesenchymal transition (EMT) may play an important role in this process, but there is a lack of in vitro models that can monitor the process of EMT. Previously, researchers used human renal tubular epithelial cells (HK-2) to prepare renal tubular chips to reproduce the EMT process.
- Simulated Kidney Stone Formation
Regarding the mechanism of stone formation, previous studies have mainly drawn indirect conclusions by extracting the components of stones, lacking real kinetic factors, making it difficult to further study its mechanism. Previously, researchers cultured HK-2 in a tubular microfluidic device and monitored calcium phosphate deposition in situ under a microscope to observe the biological process of stone formation.
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Reference
- Cong, Y.; et al. Drug toxicity evaluation based on organ-on-a-chip technology: a review. Micromachines. 2020 Apr 3;11(4):381.
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