Prevention of tumor risk associated with the reprogramming of human pluripotent stem cells
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(2020) 39:100
REVIEW
Open Access
Prevention of tumor risk associated with the reprogramming of human pluripotent stem cells Kenly Wuputra1,2, Chia-Chen Ku1,2, Deng-Chyang Wu2,3, Ying-Chu Lin4, Shigeo Saito5,6* and Kazunari K. Yokoyama1,2,5*
Abstract Human pluripotent embryonic stem cells have two special features: self-renewal and pluripotency. It is important to understand the properties of pluripotent stem cells and reprogrammed stem cells. One of the major problems is the risk of reprogrammed stem cells developing into tumors. To understand the process of differentiation through which stem cells develop into cancer cells, investigators have attempted to identify the key factors that generate tumors in humans. The most effective method for the prevention of tumorigenesis is the exclusion of cancer cells during cell reprogramming. The risk of cancer formation is dependent on mutations of oncogenes and tumor suppressor genes during the conversion of stem cells to cancer cells and on the environmental effects of pluripotent stem cells. Dissecting the processes of epigenetic regulation and chromatin regulation may be helpful for achieving correct cell reprogramming without inducing tumor formation and for developing new drugs for cancer treatment. This review focuses on the risk of tumor formation by human pluripotent stem cells, and on the possible treatment options if it occurs. Potential new techniques that target epigenetic processes and chromatin regulation provide opportunities for human cancer modeling and clinical applications of regenerative medicine. Keywords: Cancer risk, Cell reprogramming, Pluripotent stem cells, Regenerative medicine, Therapeutic agents
Background The first successful mammalian reprogramming of vegetal cells to totipotent cells using the technology of nuclear transfer generated the cloned sheep “Dolly” [1]. In recent decades, the problems caused by tumorigenesis generated by oocytes (embryos) created by nuclear transfer have been underestimated. The creation of induced pluripotent stem cells (iPSCs) requires the expression of stemness-related genes, such as the combination of Oct4, Sox2, Klf4, and c-Myc (OSKM) and that of * Correspondence: [email protected]; [email protected] 5 Waseda University Research Institute for Science and Engineering, Shinjuku, Tokyo 162-8480, Japan 1 Graduate Institute of Medicine, Kaohsiung Medical University, 100 Shih-Chuan 1st Rd., San-Ming District, Kaohsiung 807, Taiwan Full list of author information is available at the end of the article
Oct4, Sox2, Nanog and Lin28 (OSNL) [2–5]. Studies of the risk of tumorigenesis and cancerous transformation have considered somatic cell reprogramming in the context of cancer patient-specific reprogramming [2–12]. Stem cells are putative candidates for cancerous transformation given their ability to self-renew and to dedifferentiate, which can lead to the acquisition of both the genetic and epigenetic modifications required for tumorigenesis [13, 14]. The stemness-related transcription factors are expressed in
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