in vitro “human” model

Pharmaceutical companies need to screen a large number of drug candidates before developing a new medicine; this is a time-consuming process. At present, drug development costs at least 100 billion yen and requires over 10 years, since it involves screening, animal tests, and clinical trials, before the drugs can be marketed. In addition, most drugs fail during clinical trials due to their toxicity. This is because of the lack of sufficient and suitable pre-clinical trials (i.e., cell-based assays and animal tests) that are required to understand the efficacy and toxicity of drug candidates. In general, cell-based assays are used with established cell lines, which cannot be considered representative of primary cells harvested from a human body. Furthermore, although we know that drug metabolites from a tissue might reach to the other organ(s) via blood stream and cause tissue damages as drug side effects, we don’t have an in vitro method to predict such issues. It is also clear that animal systems cannot be used to represent human systems. Therefore, there is a need to establish new methods for use in pre-clinical trials as an alternative to conventional cell-based assays and animal tests.

Drug discovery/screening and toxicological tests are most suitable for applications that utilize human pluripotent stem cells (hPSCs). Various types of “human” cells with the same genomic information can be derived from cells obtained from a single source. Because hPSCs have unlimited self-renewal and differentiation ability, sufficient numbers of human tissue cells can be obtained for screening. Therefore, many pharmaceutical companies are attempting to use hPSCs for drug development/screening, and they are the one to be used in the development of the “Body on a Chip.”

I aim to develop a “Body on a Chip,” in which multiple tissue cells derived from hPSCs will be integrated into a single microfluidic device. By interconnecting multiple tissue cells with microfluidic flow channels cultured using endothelial cells derived from hPSCs, I will re-create a circulation system, which will allow monitoring of the metabolic activities in multiple tissues. First, we will create individual 3D microtissues differentiated from hPSCs, and then interconnect them. I will then increase the number of different tissues to increase the complexity, which will mimic the physiological conditions in the human body. Thus, the “Body on a Chip” will almost resemble the human body. The ultimate goal of this project is to understand the mechanisms of human body construction by mimicking life processes in a microfluidic device. Furthermore, to facilitate progress in developing the “Body on a Chip,” I propose an interdisciplinary approach that integrates micro/nanotechnology and materials science to create artificial cellular microenvironments, to examine cells and their functions of interest.