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Tumorigenicity as a clinical hurdle for pluripotent stem cell therapies

Abstract

Human pluripotent stem cells (PSCs) are a leading candidate for cell-based therapies because of their capacity for unlimited self renewal and pluripotent differentiation. These advances have recently culminated in the first-in-human PSC clinical trials by Geron, Advanced Cell Technology and the Kobe Center for Developmental Biology for the treatment of spinal cord injury and macular degeneration. Despite their therapeutic promise, a crucial hurdle for the clinical implementation of human PSCs is their potential to form tumors in vivo. In this Perspective, we present an overview of the mechanisms underlying the tumorigenic risk of human PSC–based therapies and discuss current advances in addressing these challenges.

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Figure 1: Tumorigenic hurdles to clinical translation of PSC-based therapies.
Figure 2: Potential mechanisms for tumorigenicity during the induction of pluripotency in somatic cells.

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Acknowledgements

We thank A. Morris and J. Wha-Rhee for preparing the illustrations. Because of space constraints, we were unable to include all relevant studies regarding the tumorigenicity of pluripotent stem cells; we apologize to those investigators whose valuable work we have omitted. This work was supported in part by US National Institutes of Health grants HL093172, HL099117 and EB009689, the Burroughs Wellcome Fund Career Award in the Biomedical Sciences, American Heart Association grant EIA14420025 and California Institute of Regenerative Medicine (CIRM) grants DR2-05394 and TR3-05556 (J.C.W.); CIRM Tools & Technology II (I.L.W.); a Bio-X graduate student fellowship (A.S.L.); and Howard Hughes Medical Institute research training fellowships (A.S.L. and C.T.).

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Correspondence to Mahendra S Rao, Irving L Weissman or Joseph C Wu.

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Lee, A., Tang, C., Rao, M. et al. Tumorigenicity as a clinical hurdle for pluripotent stem cell therapies. Nat Med 19, 998–1004 (2013). https://doi.org/10.1038/nm.3267

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