Human embryonic stem cells

In November of last year, groups in the United States led by James Thomson and John Gearhart published data describing the derivation of candidate human pluripotent embryonic stem (ES) and embryonic germ (EG) cell lines from blastocysts or primordial germ cells, respectively (Thomson et al., 1998; Shamblott et al., 1998). Readers will probably agree that few if any previous scientific papers reporting the characterisation of cultured cell lines would have attracted a similar degree of public attention. The interest stems in part from the ethical controversy surrounding the origins of the cells but chiefly from the widespread conviction that their availability will profoundly alter our approaches to many problems in human biology and medicine. Several features define ES cells (below), but the two key properties that make these cells so remarkable are these: ES cells can be grown in vitro and expanded in number indefinitely in the primitive undifferentiated state characteristic of the embryonic cells from which they are derived, and throughout long periods of cultivation in vitro they retain a key property of those embryonic cells – pluripotency, or the ability to develop into any cell type in the adult body (Fig. 1). The scope of even the more obvious applications envisioned for human cells with these properties is breathtaking: new approaches to the study of human embryonic development and disorders thereof, such as birth defects and embryonal tumours; access to hitherto-unexplored territories of human embryonic gene expression for modern genomics data mining; new tools for the discovery of polypeptide growth and differentiation factors that might find application in tissue regeneration and repair; new means to creating human disease models in vitro for basic research, drug discovery and toxicology; a potential answer to the issue of the chronic shortage of tissue for transplantation in the treatment of degenerative diseases, and an end to the use of immunosuppressive therapy in transplantation, if cloning techniques can be used to derive stem cells from a patient’s own tissue; new delivery systems for gene therapy. Given the potential applications of these cells, and the ethical controversy regarding the use of in vitro fertilised embryos or tissue from aborted foetuses to derive them, the widespread public discussion of these issues is understandable, warranted, and welcome. However, since the sheer volume of commentary on human ES cell ethics, scientific applications and commercial potential now threatens to overwhelm the peer-reviewed scientific literature on the subject, we will focus here on human ES cells themselves: the background to their discovery, their known properties, and what we need to learn about them before we begin to use them to address the futuristic agenda outlined above.