Abstract
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.
Highlights
Induced pluripotent stem cells can be generated directly from patient-derived somatic cells by introducing defined sets of key transcription factors [1,2,3]. iPSCs can be potentially differentiated into many cell types in our body
Sugiura et al generated iPSC clones from mouse embryonic fibroblasts (MEFs) prepared from embryo to minimize pre-existing mutations, and performed whole genome sequencing (WGS) analysis to reveal that hundreds of point mutations occur immediately after the onset of iPSC reprogramming
Mutations could arise during differentiation of iPSCs to final cell products to be used for transplantation
Summary
Induced pluripotent stem cells (iPSCs) can be generated directly from patient-derived somatic cells by introducing defined sets of key transcription factors [1,2,3]. iPSCs can be potentially differentiated into many cell types in our body. In 2014, the first-in-human clinical trial of iPSC-based cell therapy was conducted. Genetic mutations were identified in the iPSCs which were supposed to be used in the second human clinical trial of iPSC-based therapy in 2015 [9, 10]. We outline the safety issues of iPSC-based cell therapies, and further discuss how to monitor and reduce genomic instability of iPSCs. we first introduce methods to detect genomic instability of iPSCs, and describe each type of genetic variations identified in iPSCs using these methods. Many common chromosomal aberrations are reported, different types of chromosomal aberrations are identified [19, 20] The reason for these differences remains to be elucidated (for review see Lund et al [25])
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