PMID- 34944048 OWN - NLM STAT- MEDLINE DCOM- 20220107 LR - 20220107 IS - 2073-4409 (Electronic) IS - 2073-4409 (Linking) VI - 10 IP - 12 DP - 2021 Dec 15 TI - Clever Experimental Designs: Shortcuts for Better iPSC Differentiation. LID - 10.3390/cells10123540 [doi] LID - 3540 AB - For practical use of pluripotent stem cells (PSCs) for disease modelling, drug screening, and regenerative medicine, the cell differentiation process needs to be properly refined to generate end products with consistent and high quality. To construct and optimize a robust cell-induction process, a myriad of cell culture conditions should be considered. In contrast to inefficient brute-force screening, statistical design of experiments (DOE) approaches, such as factorial design, orthogonal array design, response surface methodology (RSM), definitive screening design (DSD), and mixture design, enable efficient and strategic screening of conditions in smaller experimental runs through multifactorial screening and/or quantitative modeling. Although DOE has become routinely utilized in the bioengineering and pharmaceutical fields, the imminent need of more detailed cell-lineage specification, complex organoid construction, and a stable supply of qualified cell-derived material requires expedition of DOE utilization in stem cell bioprocessing. This review summarizes DOE-based cell culture optimizations of PSCs, mesenchymal stem cells (MSCs), hematopoietic stem cells (HSCs), and Chinese hamster ovary (CHO) cells, which guide effective research and development of PSC-derived materials for academic and industrial applications. FAU - Yasui, Ryota AU - Yasui R AD - Department of Regenerative Medicine, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan. AD - Fundamental Research Laboratory, Eiken Chemical Co., Ltd., Tochigi 329-0114, Japan. FAU - Sekine, Keisuke AU - Sekine K AUID- ORCID: 0000-0001-5133-0876 AD - Department of Regenerative Medicine, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan. AD - Laboratory of Cancer Cell Systems, National Cancer Center Research Institute, Tokyo 104-0045, Japan. FAU - Taniguchi, Hideki AU - Taniguchi H AD - Department of Regenerative Medicine, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan. AD - Division of Regenerative Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan. LA - eng GR - None/Japan Agency for Medical Research and Development/ GR - 18K19589/Ministry of Education, Culture, Sports, Science and Technology of Japan/ PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20211215 PL - Switzerland TA - Cells JT - Cells JID - 101600052 SB - IM MH - Animals MH - *Cell Differentiation MH - Cell Proliferation MH - Decision Trees MH - Humans MH - Induced Pluripotent Stem Cells/*cytology MH - Research Design PMC - PMC8700474 OTO - NOTNLM OT - Chinese hamster ovary (CHO) cell OT - cell differentiation OT - design of experiments (DOE) OT - embryonic stem cell (ESC) OT - hematopoietic stem cell (HSC) OT - induced pluripotent stem cell (iPSC) OT - mesenchymal stem cell (MSC) COIS- R.Y. is employee of Eiken Chemical Co., Ltd. Authors declare no conflict of interest. EDAT- 2021/12/25 06:00 MHDA- 2022/01/08 06:00 PMCR- 2021/12/15 CRDT- 2021/12/24 01:04 PHST- 2021/11/16 00:00 [received] PHST- 2021/12/10 00:00 [revised] PHST- 2021/12/11 00:00 [accepted] PHST- 2021/12/24 01:04 [entrez] PHST- 2021/12/25 06:00 [pubmed] PHST- 2022/01/08 06:00 [medline] PHST- 2021/12/15 00:00 [pmc-release] AID - cells10123540 [pii] AID - cells-10-03540 [pii] AID - 10.3390/cells10123540 [doi] PST - epublish SO - Cells. 2021 Dec 15;10(12):3540. doi: 10.3390/cells10123540.