Yasuyuki SAKAI is a professor at Department of Chemical System Engineering Graduate School of Engineering, University of Tokyo. He received Ph. Department of Chemical Engineering, Graduate School of Engineering, University of Tokyo, Japan. His current research topics are large-scale propagation/differentiation of stem cells, engineering of implantable 3D tissues/organs and development of microphysiological systems (MPS) for drugs and industrial/environmental chemicals. He has been placing particular importance on realization of good mass transfers and 3D organization of cells in vitro. During his research carrier, he published over 240 original publications. He became an AIMBE fellow as of 2012. He is a guest professor at Technological University of Compienge, France. He is also a fellow of Society for Chemical Engineers, Japan, as of 2021. He is working as an editorial board member of Biofabrication, Bio-Design and Manufacturing and Frontiers in Toxicology.

Topic title:

Gas-Permeable Membrane-Based Direct Oxygenation Enables Cellular Aerobic Respiration in Microphysiological Systems

Abstract:

To develop physiologically-relevant in vitro tissue models, we need to integrate both parenchymal and non-parenchymal mature organ cells and extracellular matrices in an in vivo-like 3D hierarchical manner. They should also be cultured under good oxygen and nutrient supply, wastes removal, perfusion of physiological culture medium, and mechanical stimulations if necessary. Among various culture environment in vitro, oxygen supply has been a historical and  forgotten problem. For example, it is underestimated that oxygen diffusion through the layer of culture medium in static plate or dish culture restrict the cellular respiration1) but remaining unsolved. We have been proposing an alternative method, that is, direct oxygenation of cells using gas-permeable membrane as such polydimethylsiloxane (PDMS). This allows cell to show spontaneous organization and high functionality through in vivo-like aerobic respiration. In particular, we can easily form 3D heterogenic multilayered tissue, “Open Organoid”, which is better compatible with perfusion MPS to observe organ-to-organ interactions. Currently, a new gas-permeable plastic material, polymethylpentene (PMP) becomes available for cell culture to realize aerobic respiration of hepatocytes and less drug adsorption leading to realizing more accurate drug metabolism profiles2). This PMP can also be used in micro-stirrer-based on-chip perfusion MPS3. This enhanced hepatocyte functions and enabled organ-to-organ interactions in cocultured with small intestine cells. This indicate that even perfused condition, such direct oxygenation is very effective to overcome almost 1/70 lower oxygen solubility of culture medium compared with that in blood. As such, gas-permeable membrane should be used more widely in various MPS to recapture in vivo-like functions and responses due through in vivo-like aerobic respiration.