Microphysiological Systems (MPS) With Perfusable Vascular Network for Pharmacological and Organogenesis Applications
Ryuji Yokokawa,
Professor, Department of Micro Engineering,
Kyoto University
Microfluidic devices have been used to answer scientific questions in
many lifescience research fields. Microphysiological systems (MPS)
mimics the functions of human biological organs and can be used to
measure physiological functions that are difficult to measure on a
culture dish. 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. 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 kidney and brain organoids for
evaluating the effect of vessels on their development. The vascular bed
chip enabled to culture a kidney organoid at the air-liquid interface
(ALI) that is required for nephrogenesis and to separately supply two
media for the organoid and vascular bed. 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.
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