Abstract:

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 in MPS: a two-dimensional method in which organ cells and vascular endothelial cells are co-cultured on the top and bottom surfaces of a porous membrane coated with an extracellular matrix, 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 [1]. Our 3D-MPS relies on angiogenesis and/or vasculogenesis of HUVECs and other ECs. Based on our previous study to anastomose a fibroblast spheroid and perfusable vessels [2], the assay method was applied to several tumor spheroids to create tumor microenvironments to evaluate the efficacy of an anti-tumor drug under a flow condition [3]. 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 [4]. 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 [5]. 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.

References

[1] R. Banan Sadeghian et al., Commun Biol, In press.

[2] Y. Nashimoto et al., Integr Biol, 9, 6, 506-518, 2017.

[3] Y. Nashimoto et al., Biomaterials, 229, 119547, 2020.

[4] Y. Kameda et al., Lab Chip, 22, 641-651, 2022.

[5] M. Shaji et al., Under review.