Abstract

From Microphysiological to Micropathophysiolocal Models

Thomas Hartung, Professor and Doerenkamp-Zbinden Chair for Evidence-based Toxicology, Director of the Center for Alternatives to Animal Testing (CAAT), Johns Hopkins Bloomberg School of Public Health

The increasing pace of technological developments of modern cell culture and their integration leads to what is called “disruptive technologies”. The development of alternatives to traditional approaches for product development and safety assessment benefits from this. The combination of cell culture with bioengineering has led to a number of technologies to make cell culture more organo-typic, such as 3D culture, human stem cell-derived systems, perfusion, co-cultures, combinations with scaffolds and sensors etc.. Increasingly, they lead to “organ-on-chip” or even multi-organ “human-on-chip” solutions. By recreating organ architecture, homeostasis of the cell environment and organ functionality, these models mirror more closely the physiological situation. The example of our human iPSC-derived brain organoids is used to illustrate this. The commercial availability of organoids also improves standardization and reproducibility. Efforts for their quality control by Good Cell Culture Practice 2.0 and emerging reporting standards further pave the way to their broad use in academia and drug discovery.