Stem cells in human reproduction.

Human stemcell researchhasmovedat a rapidpace since pluripotent human embryonic stem cells (hESC) were first derived from the inner cell mass of IVF preimplantation embryos (Thomson et al. 1998). This breakthrough generated much excitement amongst the scientific, medical, and general communities as the potential of hESC and their derivatives for novel cell-based therapies was anticipated. Immune rejection, teratoma formation, and ethical issues associated with hESC concurrently fuelled adult stem cell research, despite the more restricted differentiation repertoire of the latter. The recent discovery that mature tissue cells can be induced to a pluripotent state (induced pluripotent cells, iPS cells) with the introduction of up to four transcription factors (Takahashi et al. 2007) was heralded as a major step forward in stem cell research as iPS cells offer an endless supply of compatible cells for regenerative medicine purposes. Stem cells are defined by three main properties that distinguish them from their more differentiated progeny; self-renewal or ability to replace themselves, differentiation into one or more lineages, and high proliferative potential. Other features of adult stem cells are their rarity in tissues and their relative proliferative quiescence compared to their daughter transit amplifying cells. The microenvironment or stem cell niche is a crucial regulator of adult stem cell function in maintaining tissue homeostasis and initiating stem cell proliferation in response to tissue damage (Li & Xie 2005). Much research has focused on directing the differentiation of hESC into desired cell types for the study of developmental processes that cannot otherwise be studied in early human development. Protocols for deriving somatic lineages, cardiomyocytes, pancreatic, neuronal, and hematopoietic lineages, hepatocytes, and germ cells to name a few, have been developed. In this Focus Issue, Golos et al. (2010) summarize current knowledge on differentiating hESC into extraembryonic lineages, in particular trophectoderm and the various trophoblast lineages, as models for the study of early human placental development. This important advance overcomes ethical restrictions on the use of human embryos for in vitro studies and the limitations of studying mouse trophoblast differentiation which differs