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Acknowledgements
The authors sincerely thank Shinya Yamanaka and Kenji Osafune (CiRA, Kyoto, Japan), as well as Yasushi Kajii,
Atsushi Nakanishi, and Seigo Izumo (Takeda Pharmaceutical, Kanagawa, Japan), for supporting the collaborative
research between Takeda Pharmaceutical and CiRA (T-CiRA, Kanagawa, Japan). The authors appreciate Kensuke
Sakuma (Orizuru Therapeutics, Kanagawa, Japan) for providing help for the statistical analysis. The authors are
grateful for the technical assistance of Shintaro Hokaiwado, Ayako Makita, Miho Ohra, Aika Takahashi, and
Ayumi Osawa (all from Orizuru Therapeutics), as well as Yoshinori Okuyama, Takahiko Totani, and Takaharu
Nishiyama (from Toyo Seikan Group Holdings, Yokohama, Japan). The authors would like to express gratitude
toward Taisuke Mochida (Takeda Pharmaceutical), Noriko Tsubooka-Yamazoe, Hikaru Ueno, Hiroaki Sugiyama,
and Akifumi Yoshihara (all from Orizuru Therapeutics) for helpful discussions. This research was supported in
part by AMED under Grant Number JP21be0404008 and the iPS Cell Research Fund.
Author contributions
R.S., S.K., J.Y., and T.T. designed the study. R.S. designed and prototyped all the new equipment used in this
study. R.S. and S.K. performed experiments and analyses. R.S., S.K., and T.T. wrote the manuscript. J.Y., R.I., S.T.,
Y.I., and T.T. discussed the results and commented on the manuscript. R.I., Y.I., and T.T. supervised the study.
Competing interests This study was performed as a collaborative study between Kyoto University, Takeda Pharmaceutical Company,
and Toyo Seikan Group Holdings. T.T. is a scientific advisor of Orizuru Therapeutics. The remaining authors
declare no competing interests.
Additional information
Supplementary Information The online version contains supplementary material available at https://doi.org/
10.1038/s41598-022-09124-w.
Correspondence and requests for materials should be addressed to R.S. or T.T.
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