Embryonic Stem Cell‐Derived Hematopoietic Cells: Are they Immunocompetent?

Abstract

Bone marrow cells are well established as a source of hematopoietic cells. Alternatively, embryonic stem (ES) cells have emerged as an exciting new source of hematopoietic progenitor cells (HPCs). However, deriving immunocompetent hematopoietic cells from ES cells remains a huge challenge. The efficiency of deriving hematopoietic cells is less than 10 % and their engraftment short‐lived. In contrast, HOXB4‐transduced ES cells more readily formed CD45+ HPCs that permanently engrafted in immunodeficient mice. Our preliminary studies show that natural killer cells target ES‐cell‐derived H60‐expressing c‐kit and Sca‐1 progenitor cells, limiting their long‐term engraftment in immunocompetent mice. As expected, deletion of NK cells allowed long‐term engraftment of the HPCs. In addition, we tested whether these newly formed HPCs can establish immunity to immunodeficient mice. Surprisingly, although HOXB4 provided self‐renewal properties to the HPCs, it obliterated their ability to form lymphocytes. Our current studies are focused on identifying the transcription factors regulating lymphopoiesis and on how HOXB4 regulates these factors. More interestingly, our newly generated human inducible pluripotent stem cells appear to be very similar to blastocyst‐derived ES cells.