Hydrogel-based sealed microchamber arrays for rapid medium exchange and drug testing of cell spheroids
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Hydrogel-based sealed microchamber arrays for rapid medium exchange and drug testing of cell spheroids Shotaro Yoshida 1
&
Kensuke Sumomozawa 1 & Kuniaki Nagamine 2 & Matsuhiko Nishizawa 1,3
# Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Culturing cell spheroids in microchamber arrays is a widely used method in regenerative medicine and drug discovery while it requires laborious procedures during medium exchange and drug administration. Here, we report a simple method for the medium exchange and drug testing using a hydrogel-based sealed microchamber arrays. Owing to the high molecular permeability of poly(vinyl alcohol) hydrogel, the sealed microchamber allows nutrients and drugs in outer medium to pass through. Thus, automatic medium exchange and drug testing for all the cell spheroids inside the microchamber arrays are achieved by simply transferring the microchamber from old medium to fresh medium. Cell spheroids of human induced pluripotent stem cellderived cardiomyocytes were cultured inside the sealed microchambers, and it was confirmed that the spheroids were stably positioned inside the microchamber even after transferring 10 times. The cell spheroids showed high viability after culturing for 7 days in the sealed microchamber with the transfer-based medium exchange, which allowed cardiac maturation by simultaneous electrical stimulation. Isoproterenol, a model cardiac drug, was administrated from outside the sealed microchamber to demonstrate the feasibility of drug testing by the rapid transfer method. Keywords Hydrogel . Drug testing . Spheroid . Human induced pluripotent stem cell . Molecular permeability
1 Introduction Cell spheroids, spherical aggregates of cultured cells, are widely used to prepare tissue grafts for regenerative medicine(Atmanli and Domian 2017; Chen et al. 2017; Chong et al. 2014; Deddens et al. 2017; Fine and VunjakNovakovic 2017; Kadota et al. 2017) and pharmacological model for drug testing.(Di Baldassarre et al. 2018; Callaghan Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10544-020-00505-4) contains supplementary material, which is available to authorized users. * Shotaro Yoshida [email protected] * Matsuhiko Nishizawa [email protected] 1
Department of Finemechanics, Graduate School of Engineering, Tohoku University, 6-6-01 Aramaki-Aoba, Aoba-ku, Sendai 980-8579, Japan
2
Research Center for Organic Electronics (ROEL), Yamagata University, 4-3-16 Jonan, Yonezawa, Yamagata 992-8510, Japan
3
Division for the Establishment of Frontier Sciences of the Organization for Advanced Studies, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai 980-8577, Japan
et al. 2019; Devalla and Passier 2018; Oleaga et al. 2019) Since the size of cell spheroids should be kept within 500 μm diameter to ensure diffusive supply of nutrients into inner cells,(Matsunaga et al. 2011) each cell spheroid needs to be separately cultured to avoid adhesion and fusion. Therefore, microchambe
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