is rigorously restricted to the sites where Placenta and yolk sac from 8-to 17-day-old (E8-E17) mouse embryos/fetuses were investigated for the presence of in vitro clonogenic progenitors. At E8-E9, the embryonic body from the umbilicus caudalwards was also analysed. Fetal liver was analysed beginning on E10. At E8, between five and nine somite pairs (sp), placenta, yolk sac and embryonic body yielded no progenitors. The first progenitors appeared at E8.5 at the stage of 15 sp in the yolk sac, 18 sp in the embryonic body, 20 sp in the placenta and only at E12 in the fetal liver (absent at E10, at E11 not determined). Progenitors with a high proliferation potential that could be replated for two months, as well as the whole range of myeloid progenitors, were found at all stages in all organs. However, the earliest of these progenitors (these yielding large, multilineage colonies) were 2-4 times more frequent in the placenta than in the yolk sac or fetal liver. In the fetal liver, late progenitors were more frequent and the cellularity increased steeply with developmental age. Thus, the fetal liver, which is a recognized site for amplification and commitment, has a very different hematopoietic developmental profile from placenta or yolk sac. Placentas were obtained from GFP transgenic embryos in which only the embryonic contribution expressed the transgene. 80% of the colonies derived from these placental cells were GFP + , and so originated from the fetal component of the placenta. These data point to the placenta as a major hematopoietic organ that is active during most of pregnancy.

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This research provides evidence that human periodontal ligament, in addition to its mesodermal derivatives, produces neural crest-like cells. Such features suggest a recapitulation of their embryonic state. The human periodontal ligament revealed itself as a viable alternative source for possible primitive precursors to be used in stem-cell therapies.