Bo Chen

Abstract: It is well believed that human embryonic stem cells (hESCs [1]) and induced pluripotent stem cells (hiPSCs [2]) are of great potential use for tissue substitutes (for example, blood cells) and to cure various congenital disorders. In mammals, hematopoiesis has already been precisely described in murine system but not yet in human. Early development of hematopoietic system can be well defined by a series of waves from primitive hematopoiesis (early embryogenesis) to definitive ones (late fetal stages). In vitro induction of undifferentiated hESC to functionally mature blood cells may mimic the early hematopoietic development during human embryonic and fetal stages. It also provides an ideal model to uncover molecular and cellular mechanisms controlling early development of human hematopoiesis. On the other hand, functionally matured blood cells derived from hESC/hiPSCs are expected to be widely used for clinical cellular therapies. Although almost all kinds of the mature blood cells can be generated from hESCs, there still lacks solid evidence for the generation of reconstituting hematopoietic stem cells (HSCs) from hESC or hiPSC. So far until now, in vitro hESC-derived blood cells possess phenotypical maturity and partial functions while still more or less share embryonic/fetal characteristics, differing greatly from their adult counterparts. This indicated that in vitro culture systems are not perfect enough to exert full mature activities. Lack of knowledge about the molecular and cellular regulations in human early hematopoiesis has handicapped the development of research on hESC/hiPSC-derived hematopoiesis.