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2017 ; 5
(ä): 51-58
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Viral Vector-Based Innovative Approaches to Directly Abolishing Tumorigenic
Pluripotent Stem Cells for Safer Regenerative Medicine
#MMPMID28480304
Mitsui K
; Ide K
; Takahashi T
; Kosai KI
Mol Ther Methods Clin Dev
2017[Jun]; 5
(ä): 51-58
PMID28480304
show ga
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.
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