title: Characterization of the cell growth analysis for detection of immortal cellular impurities in human mesenchymal stem cells.
abstract: The analysis of in vitro cell senescence/growth after serial passaging can be one of ways to show the absence of immortalized cells, which are frequently tumorigenic, in human cell-processed therapeutic products (hCTPs). However, the performance of the cell growth analysis for detection of the immortalized cellular impurities has never been evaluated. In the present study, we examined the growth rates of human mesenchymal stem cells (hMSCs, passage 5 (P = 5)) contaminated with various doses of HeLa cells, and compared with that of hMSCs alone. The growth rates of the contaminated hMSCs were comparable to that of hMSCs alone at P = 5, but significantly increased at P = 6 (0.1% and 0.01% HeLa) or P = 7 (0.001% HeLa) within 30 days. These findings suggest that the cell growth analysis is a simple and sensitive method to detect immortalized cellular impurities in hCTPs derived from human somatic cells.
authors.affiliation: Division of Medical Devices, National Institute of Health Sciences, 1-18-1 Kami-yoga, Setagaya, Tokyo 158-8501, Japan. Electronic address: kenkono@nihs.go.jp.
authors.forename: Ken
authors.initials: K
authors.lastname: Kono
authors.affiliation: Division of Cellular & Gene Therapy Products, National Institute of Health Sciences, 1-18-1 Kami-yoga, Setagaya, Tokyo 158-8501, Japan; Research on Disease Bioresources, Platform of Therapeutics for Rare Disease and Health Policy, National Institute of Biomedical Innovation, Kobe International Business Center Rm#602, 5-5-2 Minatojima-Minami-Machi, Chuo-ku, Kobe, Hyogo 650-0047, Japan. Electronic address: takada.n@nihs.go.jp.
authors.forename: Nozomi
authors.initials: N
authors.lastname: Takada
authors.affiliation: Division of Cellular & Gene Therapy Products, National Institute of Health Sciences, 1-18-1 Kami-yoga, Setagaya, Tokyo 158-8501, Japan; Foundation for Biomedical Research and Innovation, Hyogo, Japan. Electronic address: yasuda@nihs.go.jp.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yasuda
authors.affiliation: Division of Medical Devices, National Institute of Health Sciences, 1-18-1 Kami-yoga, Setagaya, Tokyo 158-8501, Japan. Electronic address: rsawada@nihs.go.jp.
authors.forename: Rumi
authors.initials: R
authors.lastname: Sawada
authors.affiliation: Division of Medical Devices, National Institute of Health Sciences, 1-18-1 Kami-yoga, Setagaya, Tokyo 158-8501, Japan. Electronic address: niimi@nihs.go.jp.
authors.forename: Shingo
authors.initials: S
authors.lastname: Niimi
authors.affiliation: Research on Disease Bioresources, Platform of Therapeutics for Rare Disease and Health Policy, National Institute of Biomedical Innovation, Kobe International Business Center Rm#602, 5-5-2 Minatojima-Minami-Machi, Chuo-ku, Kobe, Hyogo 650-0047, Japan. Electronic address: akifumi-matsuyama@umin.ac.jp.
authors.forename: Akifumi
authors.initials: A
authors.lastname: Matsuyama
authors.affiliation: Division of Cellular & Gene Therapy Products, National Institute of Health Sciences, 1-18-1 Kami-yoga, Setagaya, Tokyo 158-8501, Japan; Foundation for Biomedical Research and Innovation, Hyogo, Japan; Department of Quality Assurance Science for Pharmaceuticals, Graduate School of Pharmaceutical Sciences, Nagoya City University, Aichi, Japan; Department of Cellular & Gene Therapy Products, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan; Department of Translational Pharmaceutical Sciences, Graduated School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan. Electronic address: yoji@nihs.go.jp.
authors.forename: Yoji
authors.initials: Y
authors.lastname: Sato
mesh_terms: D018929:Cell Culture Techniques / Q000379:methods*; D006367:HeLa Cells; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology*
keywords: Cellular therapy; Mesenchymal stem cell; Quality; Regenerative medicine; Safety; Tumorigenicity