Stem cells today: A. Origin and potential of embryo stem cells.

The study of embryo stem cells began in 1963, initially using disaggregates of cleaving rabbit and mouse embryos. Their differentiation in vitro was modest, and usually curtailed at best to the formation of trophectoderm cells, which attached to plastic. Rabbit morulae and blastocysts adhered more readily, trophectoderm forming a sheet of cells which was overgrown by stem cells from inner cell mass. Whole-blastocyst cultures on collagen-coated surfaces produced a pile of cells, and its outgrowths included neural, blood, neuronal, phagocytic and many other types of cell. When inner cell mass was freed and cultured intact or as cell disaggregates, lines of embryo stem cells (ES) were established which possessed good rates of cleavage, and immense stability in their secretion of enzymes, morphology and chromosomal complement. Developmental capacities of single mouse embryo stem cells were measured by injecting one or more into a recipient blastocyst, and extent of colonization in resulting chimaeras measured their pluripotency. In mouse, cell clumps were termed embryoid bodies, which produced similar outgrowths as in rabbit. Component cells again differentiated widely, depending to a limited extent on their exposure to various cytokines or substrates. Markers for differentiation or pluripotency were established, which revealed how neural, cardiac, haematological and other ES lines could be established in vitro. These have proved useful to study early differentiation and their use in grafting to sick recipients. Displaying similar properties, human ES cells emerged in the late 1990s. Models for the clinical use of ES cells showed how they colonized rapidly, travelled to target tissues via fetal pathways, differentiated and colonized target organs. No signs of inflammation or tissue damage were noted; injured tissues could be repaired including remyelination, and no cancers were formed. ES cells offer wide therapeutic potentials for humans, although extensive clinical trials are still awaited.