Dissertation
Development of a Kidney-on-a-Chip Model for Compound Screening and Transport Studies
Pharmaceutical companies, governments and the general public have become increasingly aware that animal models used in drug testing lack vital aspects to serve as an accurate representation of human biology. As models of the human body should become more physiologically relevant, animal models no longer suffice because responses of animal cells often differ from human cells.
- Author
- M.K. Vormann
- Date
- 09 September 2021
- Links
- Thesis in Leiden Repository
Pharmaceutical companies, governments and the general public have become increasingly aware that animal models used in drug testing lack vital aspects to serve as an accurate representation of human biology. As models of the human body should become more physiologically relevant, animal models no longer suffice because responses of animal cells often differ from human cells. Instead, in vitro cell culture models with 3D architecture, microfluidics and high throughput capabilities are a promising technology. These 3D models can be developed in ways that they will likely surpass animal models on important aspects like resemblance to a human body, predicting compound safety and efficacy, high throughput testing capabilities, ethical aspects, and costs.To demonstrate the feasibility of an advanced 3D in vitro model, we used a microfluidic in vitro platform to develop a kidney-on-a-chip platform which possess the ability to reproduce the tubular response to known and unknown nephrotoxicants and compounds as seen in in vitro and in clinical studies. Furthermore, we assessed the response of the model to renal ischemia/reperfusion injury and could measure the prevention of tubular damage when adding protective compounds.These findings show that 3D tissue models can compete with alternatives like animal models and 2D models.