With as many as 90% of new drug compounds falling short in clinical trials, the journey from a promising drug candidate to a marketable medication is fraught with challenges and uncertainties. This high attrition rate is not only costly for drug developers, but also hinders access to better and potentially life-saving treatments for patients. Even with innovative tools such as artificial intelligence, machine learning, 3D cell cultures, and omics-based technologies, the prevalence of drug failures continues to cast a shadow on the promise of breakthrough therapies.
Due to their ease-of-use and scalability, in vitro 2D cell culture models are useful in drug screening applications. But they can fail to properly replicate in vivo human biological settings, leading to promising early results that fizzle out in later clinical stages. Animal models also oftentimes fail to predict clinical response in humans and raise concerns about the animals’ welfare while being costly and time-consuming. It has become clear that more robust models are needed to ensure a seamless transition for promising drug candidates to become efficacious medications for patients.
Introducing organ-on-chip platforms
Organ-on-chip (OOC) models have emerged as a promising alternative, possibly overcoming some of the limitations of animal experiments. An OOC is a microfluidic device containing hollow channels lined with living cells, which are often derived from human tissues or stem cells, to form miniature organ-like structures. The cells can interact with each other and the microenvironment to mimic functional units of specific organs.
The primary goal of OOC technology is to replicate the complex microenvironment of human organs in vitro, allowing researchers to study diverse physiological processes, test drugs, and gain insights into human biology. One of the attractive features of OOC devices is their ability to reproduce mechanical forces and physical characteristics unique to each organ. For example, lung-on-chip devices may simulate breathing motions, while heart-on-chip devices may replicate the heart’s rhythmic contractions.
Predicting toxicity with organ-on-chip
Because the failure of many drug candidates is often attributed to their toxicity in humans, with the liver and kidneys being common sites of adverse effects, leveraging OOCs in drug safety assessments allows researchers to closely mimic the physiological conditions of these vital organs in vitro. Utilizing a liver-on-chip, Ewart et al. have used the Opera PhenixTM system to predict drug-induced liver injury (DILI) with very high accuracy.
Kidneys can also suffer from drug-induced damage (termed nephrotoxicity), so kidney OOCs offer similar potential benefits to test out early stage toxicity to avoid setbacks and costs in late stages. This approach can provide valuable insights into potential toxicities and help identify compounds with improved safety profiles early in the drug development process.
Read the literature review to learn more about the latest findings and future outlook of liver and kidney OOC models.
For research use only. Not for use in diagnostic procedures
