Abstract：
:Generation of human-induced pluripotent stem cells (iPSCs) from somatic cells has opened the possibility to design novel therapeutic approaches. In 2014, the first-in-human clinical trial of iPSC-based therapy was conducted. However, the transplantation for the second patient was discontinued at least in part due to genetic aberrations detected in iPSCs. Moreover, many studies have reported genetic aberrations in iPSCs with the rapid progress in genomic technologies. The presence of genomic instability raises serious safety concerns and can hamper the advancement of iPSC-based therapies. Here, we summarize our current knowledge on genomic instability of iPSCs and challenges in their clinical applications. In view of the recent expansion of stem cell therapies, it is crucial to gain deeper mechanistic insights into the genetic aberrations, ranging from chromosomal aberrations, copy number variations to point mutations. On the basis of their origin, these genetic aberrations in iPSCs can be classified as (i) preexisting mutations in parental somatic cells, (ii) reprogramming-induced mutations, and (iii) mutations that arise during in vitro culture. However, it is still unknown whether these genetic aberrations in iPSCs can be an actual risk factor for adverse effects. Intersection of the genomic data on iPSCs with the patients' clinical follow-up data will help to produce evidence-based criteria for clinical application. Furthermore, we discuss novel approaches to generate iPSCs with fewer genetic aberrations. Better understanding of iPSCs from both basic and clinical aspects will pave the way for iPSC-based therapies.
journal_name
Adv Exp Med Bioljournal_title
Advances in experimental medicine and biologyauthors
Yoshihara M,Oguchi A,Murakawa Ydoi
10.1007/978-3-030-31206-0_2subject
Has Abstractpub_date
2019-01-01 00:00:00pages
23-47eissn
0065-2598issn
2214-8019journal_volume
1201pub_type
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更新日期：2016-01-01 00:00:00
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abstract：:Drosophila melanogaster is since decades the most important invertebrate model. With the publishing of the genome sequence, Drosophila also became a pioneer in (neuro)peptide research. Neuropeptides represent a major group of signaling molecules that outnumber all other types of neurotransmitters/modulators and hormon...
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pub_type： 杂志文章,评审
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更新日期：2010-01-01 00:00:00
