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. 2013 Aug;19(8):998-1004.
doi: 10.1038/nm.3267. Epub 2013 Aug 6.

Tumorigenicity as a Clinical Hurdle for Pluripotent Stem Cell Therapies

Free PMC article

Tumorigenicity as a Clinical Hurdle for Pluripotent Stem Cell Therapies

Andrew S Lee et al. Nat Med. .
Free PMC article


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.


Figure 1
Figure 1. Tumorigenic hurdles to clinical translation of pluripotent stem cell based therapies
Depicted are tumorigenic pitfalls associated with applications of pluripotent stem cells for patient treatment, using ischemic heart disease as an example. Specific areas of concern include derivation of ESCs/iPSCs, culture and differentiation into therapeutic cell populations (ie cardiomyocytes), delivery into sites of injury, and engraftment.
Figure 2
Figure 2. Potential mechanisms for tumorigenicity during induction of pluripotency in somatic cells
This figure illustrates the common mechanisms by which the process of reprogramming somatic cells to pluripotency may directly result in promotion of tumorigenic outcomes. Specifically, global epigenetic hypomethylation (purple circles) may directly cause chromosomal abnormalities and oncogene activation. Integration of pluripotency transgenes such as MYC (blue) may result in reactivation of oncogenic networks following cell differentiation and transplantation into patients. Genomic integration of transgenes may also directly inactivate tumor suppressors (white) or activate oncogenes (orange), causing abnormal cell growth.

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