The induction cf the differentiation of human embryonic stem cells into hematopoietic stem and progenitor cells.

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Human embryonic stem cells (ESC) recently established from the inner cell mass of human preimplantation embryos have the abilities to be maintained as undifferentiated cells in culture without apparent limit and to differentiate into all types of tissue cells. This property of human ESC indicates the potential application for blood medicine including cellular therapies, such as blood transfusion and hematopoietic stem cell transplantation, and the evaluation of drug effect on various blood cells in vitro.Because hematopoietic tissues play crucial roles in survival, differentiation and proliferation of hematopoietic cells, it is important to reproduce the circumstance surrounding hematopoietic cells in vitro for their development. In embryo, the development of hemotopoietic system is a complex process which sequentially occurs in several tissues, but fetal liver (FL) is the predominant source of blood cells until just before time when the hematopoiesis resides in bone marrow.We then established stromal cells from mouse FL cells and cocultured human embryonic stem cells (ESC) with them. Human ESC began to differentiate at day 6 of coculture, and generated immature hematopoietic cells at day 12. At day 16, we performed clonal cultures of these cocultured cells for 2 weeks. The human ESC-derived cells produced a number of myeloid, erythroid and multi-lineage colonies, which consist of myeloid cells including neutrophils and macrophages, erythroid cells which contain mature erythrocytes, and both, respectively. This result indicates that human ESC have the capability to generate a variety of hematopoietic progenitors which can produce mature blood cells in coculture with mouse FL-derived stromal cells. The human ESC-derived hematopoietic progenitors can be a novel source for the cells applicable to various cellular therapies.