The origins of human pluripotent stem cells: the road from a cancer to regenerative medicine

The notion of using pluripotent stem cells (PSCs) as a source of differentiated cell types for replacement of disease or damaged tissues in regenerative medicine is now an active area of research, with approaches to treating eye diseases such as age-related macular degeneration or Parkinson’s disease now on the horizon. But the foundations for this research lie in a quite different area of science, namely the role of genetics of cancer. In this review, we trace the evolution of ideas starting with the discovery that strain 129 mice are particularly subject to develop germ cell tumors, through the identification of embryonal carcinoma (EC) cells as the stem cells of the teratocarcinoma manifestation of these tumors, to the recognition of their relationship to pluripotent cells of the early embryo, and eventually their role in the derivation of embryonic stem cells, first from mouse embryos and then from primates including humans. This is a story that illustrates how science commonly develops through the interests and insights of individual investigators, often with unexpected and unintended outcomes.