IntroductionMultipotential mesenchymal stem/progenitor cells (MSCs) can be induced to differentiate into bone, adipose, cartilage, muscle, and endothelium if these cells are cultured under specific permissive conditions [1,2]. In rodents, a specific type of MSC (termed multipotent adult progenitor cell) can be isolated from bone marrow (BM) and contributes to most somatic cell types when injected into early blastocysts at the single-cell level [3] , kidney, lung, and liver). These cells are also present in the fetal environment (e.g., blood, liver, BM, and kidney). However, MSCs are a rare population in these tissues. Here we tried to identify cells with MSC-like potency in human placenta. We isolated adherent cells from trypsin-digested term placentas and established two clones by limiting dilution. We examined these cells for morphology, surface markers, gene expression patterns, and differentiation potential and found that they expressed several stem cell markers, hematopoietic/ endothelial cell-related genes, and organ-specific genes, as determined by reverse transcription-polymerase chain reaction and fluorescence-activated cell sorter analysis. They also showed osteogenic and adipogenic differentiation potentials under appropriate conditions. We suggest that placenta-derived cells have multilineage differentiation potential similar to MSCs in terms of morphology, cell-surface antigen expression, and gene expression patterns. The placenta may prove to be a useful source of MSCs.

Erythropoiesis is characterized by 2 waves of production during mouse embryogenesis: a primitive one originating from the yolk sac (YS) and a definitive one produced from both the YS and the embryo proper. How the latter wave is generated remains unclear. To investigate our hypothesis that endothelial cells (ECs) could generate erythroid cells, we designed a method to label ECs at 10 days after coitus. This labeling method associates 2 techniques: an intracardiac inoculation that allows molecules to be delivered into the bloodstream followed by a whole-embryo culture period. DiI-conjugated acetylated low-density lipoproteins (Ac-LDL-DiI) were used to specifically tag ECs from the inside. One hour after inoculation, DiI staining was found along the entire endothelial tree. Fluorescenceactivated cell sorter (FACS) analysis revealed that DiI ؉ cells were CD31 ؉ , CD34 ؉ , and CD45 ؊ , an antigen makeup characteristic of the endothelial lineage. Twelve hours after inoculation, 43% of DiI ؉ circulating cells belonged to the erythroid lineage. These cells expressed Ter119 and displayed an adult globin chain arrangement; thus they belonged to the definitive lineage as confirmed in erythroid colony formation. IntroductionDuring mouse embryogenesis, hematopoiesis begins in the extraembryonic yolk sac (YS) at 7.5 days after coitus (dpc), shifting to fetal liver at midgestation, then to spleen, and finally to bone marrow shortly before birth. Classical embryological experiments, clonal culture assays, and genetic studies in the mouse have demonstrated the existence of 2 distinct waves of hematopoietic emergence: a transient one, mainly restricted to erythropoiesis occurring in the YS blood islands prior to circulation between YS and embryo, and a definitive one originating from both the YS and the embryo proper. Consistent with pioneer studies on the avian model, the embryonic site has been identified in the aortic region-the so-called para-aortic splanchnopleura (p-Sp)/aortagonad-mesonephros (AGM) region-and was shown to be capable of producing hematopoietic cells (HCs) including hematopoietic stem cells (HSCs). 1,2 In addition, in both avian and mouse species, the YS was shown to be able to produce definitive HSCs, including cells of erythroid lineage, at the same time as or even slighly before the AGM formation. [3][4][5][6][7][8] Primitive and definitive erythropoiesis yields mature erythrocytes distinguishable by their morphology and the hemoglobin types they express. Mature primitive erythrocytes are nucleated cells containing embryonic as well as adult hemoglobins, whereas mature definitive erythrocytes are smaller enucleated red blood cells committed to adult hemoglobin synthesis. [9][10][11] In the YS as well as in the aorta, HCs and ECs develop in close association. This proximity has prompted earlier embryologists to assume the existence of a putative ancestral mesodermal progenitor for ECs and HCs, the so-called hemangioblast. 12 In addition to the shared expression of several markers, gene targeting experimen...