Viral Vector-Based Innovative Approaches to Directly Abolishing Tumorigenic Pluripotent Stem Cells for Safer Regenerative Medicine.
Viral Vector-Based Innovative Approaches to Directly Abolishing Tumorigenic Pluripotent Stem Cells for Safer Regenerative Medicine.
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DOI：
10.1016/j.omtm.2017.03.002
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发表时间：
2017-06-16
期刊：
影响因子：
--
通讯作者：
Kosai KI
中科院分区：
文献类型：
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作者：
Mitsui K;Ide K;Takahashi T;Kosai KI
人类多能干细胞（hPSCs）是临床应用中有前景的再生材料来源。然而，hPSC移植疗法存在形成畸胎瘤以及未分化残留细胞恶性转化的风险。这些问题凸显了开发完全防止肿瘤发生的技术以确保临床安全应用的重要性。到目前为止的研究有助于建立安全的hPSC细胞系，提高分化诱导的效率，并间接确保产品的安全性。尽管做出了这些努力，保证再生医学产品的临床安全性仍然是一个关键挑战。鉴于hPSCs固有的基因组不稳定性、癌细胞的选择性生长优势以及先前造血干细胞基因治疗尝试失败所吸取的教训，传统策略不太可能完全克服与hPSC肿瘤发生相关的问题。研究人员最近开始了旨在定位和直接治疗hPSC衍生的致瘤细胞的研究。特别是，通过转导自杀基因和溶瘤病毒直接杀死致瘤细胞的新方法有望提高基于hPSC的疗法的安全性。本文讨论了旨在直接根除未分化的致瘤性hPSCs的方法的现状和未来展望，重点是病毒载体转导。
Human pluripotent stem cells (hPSCs) are a promising source of regenerative material for clinical applications. However, hPSC transplant therapies pose the risk of teratoma formation and malignant transformation of undifferentiated remnants. These problems underscore the importance of developing technologies that completely prevent tumorigenesis to ensure safe clinical application. Research to date has contributed to establishing safe hPSC lines, improving the efficiency of differentiation induction, and indirectly ensuring the safety of products. Despite such efforts, guaranteeing the clinical safety of regenerative medicine products remains a key challenge. Given the intrinsic genome instability of hPSCs, selective growth advantage of cancer cells, and lessons learned through failures in previous attempts at hematopoietic stem cell gene therapy, conventional strategies are unlikely to completely overcome issues related to hPSC tumorigenesis. Researchers have recently embarked on studies aimed at locating and directly treating hPSC-derived tumorigenic cells. In particular, novel approaches to directly killing tumorigenic cells by transduction of suicide genes and oncolytic viruses are expected to improve the safety of hPSC-based therapy. This article discusses the current status and future perspectives of methods aimed at directly eradicating undifferentiated tumorigenic hPSCs, with a focus on viral vector transduction.