Growth of Teratomas Derived from Human Pluripotent Stem Cells Is Influenced by the Graft Site

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Abstract
Pluripotent stem cells transplanted into immune-deficient mice form complex teratomas. Although such tumors are generally haphazard in their organization, they do contain some structures that resemble tissues normally seen in the embryo. As a consequence, the teratoma model is useful for exploring the developmental potential of stem cells and studying certain aspects of tissue development. To further our understanding of this process, we examined whether the anatomical location into which human pluripotent stem cells were grafted influenced their growth in situ. Here we report that cells grafted into the liver rapidly produced large tumors containing predominantly immature cells. In contrast, subcutaneous implants were significantly slower growing and eventually formed tumors composed of differentiated tissues. The alternative growth patterns recorded between these two graft sites indicates how environmental cues affect stem cell behavior. This approach may lead to the identification of new ways to control stem cell growth and differentiation.