Generation of transplantable hematopoietic stem cells based from human embryonic stem cells

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We proposed a novel method for the efficient production of hematopoietic progenitors from human embryonic stem cells (hESC) by co-culturing with stromal cells derived from murine fetal liver, in which embryonic hematopoiesis drastically expands at midgestation. In the co-culture, various hematopoietic progenitors were generated, and this hematopoietic activity was concentrated in cobblestone-like cells derived from differentiated hESC. The cobblestone-like cells mostly expressed CD34 and retained an endothelial potential. They also contained hematopoietic colony-forming cells, especially erythroid and multilineage colony-forming cells at high frequency. The multipotential hematopoietic progenitors abundant among the cobblestone-like cells produced almost all types of mature blood cells, including adult-type b globin-expressing erythrocytes and tryptase/chymase double-positive mast cells. They showed neither immature properties of ESC nor the potential to differentiate into endoderm and ectoderm at a clonal level. The developed co-culture system of hESC can provide a novel source for hematopoietic and blood cells applicable to cellular therapies and drug screenings.