![]() ![]() Para-aortic splanchnopleural regions that will develop into aorta–gonad–mesonephros (AGM) already possess hematopoietic precursors beginning at 8.5 dpc. The first hematopoiesis (primitive hematopoiesis) begins to develop primitive erythroid and macrophage progenitors in the yolk sac (YS) blood islands at 7.0 dpc. The hematopoietic system that derives from the mesodermal germ layer can be classified into two waves. In mouse blastocyst, the inner cell mass at 3.5 days post coitum (dpc) comprises a population of cells – which can give rise to a derivative of three germ layers (endoderm, mesoderm and ectoderm) – that eventually develop into both intraembryonic and extraembryonic tissues as embryo develops. Studies of hematopoietic development during embryogenesis in vivo are important to gain insight into its underlying mechanisms, whereby accumulated knowledge will facilitate the induction of HSCs, hematopoietic progenitor cells (HPCs) and mature hematopoietic cells from pluripotent stem cells in culture. To review current progress of differentiation protocol from ES/iPS cells, we first summarize the knowledge of hematopoietic development during early mouse hematopoiesis followed by the manipulation of ES/iPS cells in hematopoietic cell induction (Figure 1). It is of great importance to develop efficient and controllable induction strategies to drive hematopoietic differentiation from ES/iPS cells in culture prior to the realization of pluripotent cell-derived therapies. Induced pluripotent stem (iPS) cell technology has made a groundbreaking discovery to circumvent the problems of ethical and practical issues in using ES cells. However, manipulation of human ES cells raises some ethical issues and immunoreactions. Embryonic stem (ES) cells are pluripotent cells established from the inner cell mass of blastocyst-stage embryos, in both mouse and human, and are capable of giving rise to three germ layers after directed differentiation in culture. Pluripotent stem cells are one of the potential sources for HSCs and the in vitro model for further elucidating the regulatory mechanisms underlying embryonic hematopoietic development. The use of alternative sources for these cells will therefore be a great advantage for regenerative medicine. Additionally, problems such as shortage of human leukocyte antigen-matched donors, adverse effects from graft-versus-host disease, viral contamination and immunoreactions impede the utility of readily available HSCs. However, some conventional sources of HSCs – such as cord blood, bone marrow and peripheral blood – are limited in usage, owing to the limited number of transplantable cells as well as inefficient strategies for expanding those cells. Currently, HSC transplantation and hematopoietic cell transfusion are useful treatments for some hematological diseases, such as thalassemia and leukemia. Perturbations in the hematopoietic system have been reported to cause numerous diseases such as anemia, leukemia, lymphomas and thrombocytopenia. Hematopoietic stem cells (HSCs) lay the foundation of hematopoiesis to generate all functional hematopoietic lineages, including erythrocytes, leukocytes (neutrophils, basophils, eosinophils, lymphocytes, monocytes and macrophages) and platelets. We hereby review the current progress of hematopoietic cell induction from embryonic stem/induced pluripotent stem cells. Pluripotent stem cells are therefore extensively utilized to facilitate better understanding in hematopoietic development by recapitulating embryonic development in vivo, in which efficient strategies can be easily designed and deployed for the generation of hematopoietic lineages in vitro. Owing to a shortage of donors and a limited number of the cells, hematopoietic cell induction from pluripotent stem cells has been regarded as an alternative source of HSCs and mature hematopoietic cells for intended therapeutic purposes. Nowadays, HSC transplantation and hematopoietic cell transfusion have successfully cured some patients, especially in malignant hematological diseases. Establishment of pluripotent stem cells provides a comprehensive model to study early hematopoietic development and has emerged as a powerful research tool to explore regenerative medicine. Pluripotent stem cells, both embryonic stem cells and induced pluripotent stem cells, are undifferentiated cells that can self-renew and potentially differentiate into all hematopoietic lineages, such as hematopoietic stem cells (HSCs), hematopoietic progenitor cells and mature hematopoietic cells in the presence of a suitable culture system.
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