Robotic search for optimal cell culture in regenerative medicine

Genki N Kanda; Taku Tsuzuki; Motoki Terada; Noriko Sakai; Naohiro Motozawa; Tomohiro Masuda; Mitsuhiro Nishida; Chihaya T Watanabe; Tatsuki Higashi; Shuhei A Horiguchi; Taku Kudo; Motohisa Kamei; Genshiro A Sunagawa; Kenji Matsukuma; Takeshi Sakurada; Yosuke Ozawa; Masayo Takahashi; Koichi Takahashi; Tohru Natsume

doi:10.7554/eLife.77007

Robotic search for optimal cell culture in regenerative medicine

Elife. 2022 Jun 28:11:e77007. doi: 10.7554/eLife.77007.

Authors

Genki N Kanda^#^{1

2

3}, Taku Tsuzuki^#⁴, Motoki Terada^{1

5}, Noriko Sakai^{1

5}, Naohiro Motozawa¹, Tomohiro Masuda^{1

5}, Mitsuhiro Nishida^{1

5}, Chihaya T Watanabe⁴, Tatsuki Higashi⁴, Shuhei A Horiguchi⁴, Taku Kudo³, Motohisa Kamei³, Genshiro A Sunagawa^{1

6}, Kenji Matsukuma³, Takeshi Sakurada⁴, Yosuke Ozawa⁴, Masayo Takahashi^{1

5

7}, Koichi Takahashi^{2

8

9}, Tohru Natsume^{3

10}

Affiliations

¹ Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan.
² Laboratory for Biologically Inspired Computing, RIKEN Center for Biosystems Dynamics Research, Osaka, Japan.
³ Robotic Biology Institute Inc., Tokyo, Japan.
⁴ Epistra Inc., Tokyo, Japan.
⁵ VCCT Inc., Kobe, Japan.
⁶ Laboratory for Molecular Biology of Aging, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan.
⁷ Vision Care Inc., Kobe, Japan.
⁸ Graduate School of Media and Governance, Keio University, Fujisawa, Japan.
⁹ Graduate School of Frontier Biosciences, Osaka University, Suita, Japan.
¹⁰ Department of Life Science and Biotechnology, Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology, Tokyo, Japan.

^# Contributed equally.

Abstract

Induced differentiation is one of the most experience- and skill-dependent experimental processes in regenerative medicine, and establishing optimal conditions often takes years. We developed a robotic AI system with a batch Bayesian optimization algorithm that autonomously induces the differentiation of induced pluripotent stem cell-derived retinal pigment epithelial (iPSC-RPE) cells. From 200 million possible parameter combinations, the system performed cell culture in 143 different conditions in 111 days, resulting in 88% better iPSC-RPE production than that obtained by the pre-optimized culture in terms of the pigmentation scores. Our work demonstrates that the use of autonomous robotic AI systems drastically accelerates systematic and unbiased exploration of experimental search space, suggesting immense use in medicine and research.

Keywords: LabDroid; bayesian optimization; computational biology; human; iPS cell; laboratory automation; regenerative medicine; retinal pigment epithelium; stem cells; systems biology.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Bayes Theorem
Cell Culture Techniques / methods
Cell Differentiation
Induced Pluripotent Stem Cells*
Regenerative Medicine
Retinal Pigment Epithelium
Robotic Surgical Procedures*

Grants and funding

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.