Abstract

Cell therapy using induced pluripotent stem cell (iPSC) derivatives may result in abnormal tissue generation because the cells undergo numerous cycles of mitosis before clinical application, potentially increasing the accumulation of genetic abnormalities. Therefore, genetic tests may predict abnormal tissue formation after transplantation. Here, we administered iPSC derivatives with or without single-nucleotide variants (SNVs) and deletions in cancer-related genes with various genomic copy number variant (CNV) profiles into immunodeficient mice and examined the relationships between mutations and abnormal tissue formation after transplantation. No positive correlations were found between the presence of SNVs/deletions and the formation of abnormal tissues; the overall predictivity was 29%. However, a copy number higher than 3 was correlated, with an overall predictivity of 86%. Furthermore, we found CNV hotspots at 14q32.33 and 17q12 loci. Thus, CNV analysis may predict abnormal tissue formation after transplantation of iPSC derivatives and reduce the number of tumorigenicity tests.

Details

Title
Correlation Between Genetic Abnormalities in Induced Pluripotent Stem Cell-Derivatives and Abnormal Tissue Formation in Tumorigenicity Tests
Author
Yamamoto, Takako 1 ; Sato, Yoji 2 ; Yasuda, Satoshi 2 ; Shikamura, Masayuki 1 ; Tamura, Takashi 1 ; Takenaka, Chiemi 1 ; Takasu, Naoko 3 ; Nomura, Masaki 3 ; Dohi, Hiromi 3 ; Takahashi, Masayo 4 ; Mandai, Michiko 5 ; Kanemura, Yonehiro 6 ; Nakamura, Masaya 7 ; Okano, Hideyuki 8 ; Kawamata, Shin 9 

 R&D Center for Cell Therapy, Foundation for Biomedical Research and Innovation, Kobe, Japan 
 Division of Cell-Based Therapeutic Products, National Institute of Health Sciences, Kawasaki, Japan 
 CiRA Foundation, Kyoto, Japan 
 Riken BDR, Kobe, Japan; Vison Care Inc., Kobe, Japan 
 Riken BDR, Kobe, Japan 
 Department of Biomedical Research and Innovation, Institute for Clinical Research, National Hospital Organization Osaka National Hospital, Osaka, Japan 
 Department of Orthopedic Surgery, Keio University School of Medicine, Tokyo, Japan 
 Department of Physiology, Keio University School of Medicine, Tokyo, Japan 
 R&D Center for Cell Therapy, Foundation for Biomedical Research and Innovation, Kobe, Japan; Riken BDR, Kobe, Japan 
Pages
527-538
Publication year
2022
Publication date
May 2022
Publisher
Oxford University Press
ISSN
21576564
e-ISSN
21576580
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3191459026
Copyright
© The Author(s) 2022. Published by Oxford University Press. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.