Genomic Instability of iPSCs: Challenges Towards Their Clinical Applications.
Induced pluripotent stem cells (iPSCs) are a type of pluripotent stem cells generated directly from mature cells through the introduction of key transcription factors. iPSCs can be propagated and differentiated into many cell types in the human body, holding enormous potential in the field of regenerative medicine. However, genomic instability of iPSCs has been reported with the advent of high-throughput technologies such as next-generation sequencing. The presence of genetic variations in iPSCs has raised serious safety concerns, hampering the advancement of iPSC-based novel therapies. Here we summarize our current knowledge on genomic instability of iPSCs, with a particular focus on types of genetic variations and their origins. Importantly, it remains elusive whether genetic variations in iPSCs can be an actual risk factor for adverse effects including malignant outgrowth. Furthermore, we discuss novel approaches to generate iPSCs with fewer genetic variations. Lastly, we outline the safety issues and monitoring strategies of iPSCs in clinical settings.
Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Kanagawa, Japan.|Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Masahito
M
Yoshihara
RIKEN Preventive Medicine and Diagnosis Innovation Program, Wako, Saitama, Japan.
Yoshihide
Y
Hayashizaki
Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Kanagawa, Japan. yasuhiro.murakawa@riken.jp.|RIKEN Preventive Medicine and Diagnosis Innovation Program, Wako, Saitama, Japan. yasuhiro.murakawa@riken.jp.
Yasuhiro
Y
Murakawa
D002454:Cell Differentiation / Q000235:genetics*; D065150:Cellular Reprogramming / Q000235:genetics*; D014644:Genetic Variation; D042822:Genomic Instability; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism* / Q000637:transplantation*; D008957:Models, Genetic; D012307:Risk Factors; D033581:Stem Cell Transplantation / Q000379:methods; D014157:Transcription Factors / Q000235:genetics
D014157:Transcription Factors
Clinical application; Genomic instability; Mutation; Regenerative medicine; iPSCs