Abstract

Microphysiological Systems (MPS) With Perfusable Vascular Network for Pharmacological and Infectious Disease Applications

Ryuji Yokokawa, Professor, Department of Micro Engineering, Kyoto University

Microfluidic devices have been used to answer scientific questions in many lifescience research fields. Although applicability of microphysiological systems (MPS) to drug development attracts many researchers, MPS is also widely used to address fundamental scientific questions in biology. We have employed two approaches to create the interface between organ cells and vascular networks: a two-dimensional method in which organ cells and vascular endothelial cells are co-cultured on a porous membrane such as Transwell (2D-MPS), and a three-dimensional method in which the spontaneous patterning ability of vascular endothelial cells is utilized (3D-MPS). As an example of 2D-MPS, we developed a renal proximal tubule model and a glomerular filtration barrier model using iPSC-derived organoid cells, which enables us to evaluate reabsorption, filtration, and nephrotoxicity. It was applied to airway and alveoli models to evaluate SARS-CoV-2 and influenza infections. For 3D-MPS, angiogenesis and/or vasculogenesis are utilized to anastomose a fibroblast spheroid and tumor spheroids to create tumor microenvironments to evaluate the efficacy of an anti-tumor drug under a flow condition. We also developed an on-chip vascular bed to co-culture with any kind of tissues that do not have enough angiogenic factors to induce angiogenesis. It was applied to bronchial organoids for evaluating the infection of epithelial cells to vascular network. Proposed assay platforms will further contribute to realize pharmacological applications and to understand in vivo organogenesis. We keep exploring how micro/nano fabrications can deepen science at the interface between blood vessels and organs.