Kidney-on-a-Chip: Safer and Human-Relevant Drug Testing
The current pipeline for drug testing relies heavily on preliminary tests in animals for safety and efficacy. However, humans and animals share important differences in their physiology, and the dramatic difference of drug clearance by the kidneys is just one example. Consequently, drugs that are found to be safe and efficacious in animals may still be toxic and/or ineffective in humans, and vice versa drug candidates that are dropped due to failed trials in animal studies may actually be safe and effective in humans. Researchers at the University of Michigan recently developed a kidney-on-a-chip device that allows for drug testing on human kidney cells while mimicking the physiological flow of liquids through the human kidney. The device is created by sandwiching a thin layer of cultured human kidney cells between a permeable polyester membrane that contains miniscule channels. This device replicates the internal environment of a human kidney and precisely controls fluid flow across kidney cells. Not only does it offer more human-relevant test results for medications with much lower costs than animal models, it allows for testing in a controlled, reproducible environment and the ability to alter fluid flow to simulate a wide spectrum of kidney function levels, which is often the case with sick patients in the hospital. It can be used to optimize drug dosing, model the behavior of medications inside the body over time (i.e. pharmacokinetic profile), and simulate the drug filtering process inside kidneys. The researchers used the device to study two different methods of administering the antibiotic gentamicin and found that one method was far safer than the second even at equivalent doses. This device serves as a model to study the effects of drugs on other organs in the human body and promises to make drug testing more cost-effective and less labor-intensive. The researchers hope to further advance the device to allow for real-time drug testing, multi-drug regimen delivery, and more variety of information output of the effects on the human tissue.
References
- Kim S, LesherPerez SC, Kim BC, et al. Pharmacokinetic profile that reduces nephrotoxicity of gentamicin in a perfused kidney-on-a-chip. Biofabrication. 2016;8:015021. doi: 10.1088/1758-5090/8/1/015021.