Quality evaluation of cell spheroids for transplantation by monitoring oxygen consumption using an on-chip electrochemical device

Mari Tsujimura; Kosuke Kusamori; Kodai Takamura; Temmei Ito; Takatoshi Kaya; Kazunori Shimizu; Satoshi Konishi; Makiya Nishikawa

doi:10.1016/j.btre.2022.e00766

Quality evaluation of cell spheroids for transplantation by monitoring oxygen consumption using an on-chip electrochemical device

Biotechnol Rep (Amst). 2022 Oct 3:36:e00766. doi: 10.1016/j.btre.2022.e00766. eCollection 2022 Dec.

Authors

Mari Tsujimura¹, Kosuke Kusamori¹, Kodai Takamura¹, Temmei Ito², Takatoshi Kaya², Kazunori Shimizu³, Satoshi Konishi⁴, Makiya Nishikawa¹

Affiliations

¹ Laboratory of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan.
² KONICA MINOLTA, INC., No.1 Sakura-machi, Hino-shi, Tokyo, 191-8511, Japan.
³ Department of Biomolecular Engineering, Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi, 464-8603, Japan.
⁴ Department of Mechanical Engineering, Graduate School of Science and Engineering, Ritsumeikan University, 1-1-1 Noji-higashi, Kusatsu, Shiga, 525-8577, Japan.

Abstract

Three-dimensional cell spheroids are superior cell-administration form for cell-based therapy which generally exhibit superior functionality and long-term survival after transplantation. Here, we nondestructively measured the oxygen consumption rate of cell spheroids using an on-chip electrochemical device (OECD) and examined whether this rate can be used as a marker to estimate the quality of cell spheroids. Cell spheroids containing NanoLuc luciferase-expressing mouse mesenchymal stem cell line C3H10T1/2 (C3H10T1/2/Nluc) were prepared. Spheroids of high or low quality were prepared by altering the medium change frequency. After transplantation into mice, the high-quality C3H10T1/2/Nluc spheroids exhibited a higher survival rate than the low-quality ones. The oxygen consumption rate of the high-quality C3H10T1/2/Nluc spheroids was maintained at high levels, whereas that of the low-quality spheroids decreased with time. These results indicate that OECD-based measurement of the oxygen consumption rate can be used to estimate the quality of cell spheroids without destructive analysis of the spheroids.

Keywords: Cell spheroid; Cell-based therapy; On-chip electrochemical device; Oxygen consumption; Quality evaluation.