Immunity of Embryonic Stem Cell-derived Hematopoietic Progenitor Cells

A number of medical conditions including hematopoietic stem cell malignancies, immunodeficiencies, and autoimmune diseases can be treated using bone marrow cells. However, the major hindrance to the routine use of bone marrow cells is their unparalleled immunogenicity, requiring the use of harsh and toxic preconditioning regimens that can be fatal. Thus, identification of a safer alternative source of hematopoietic stem cells that can be broadly used in such therapies is highly desirable. Despite the current limited number of human ES cell lines, we believe that the newer technology of reprogramming adult somatic cells into pluripotent cells will eventually lead to greater availability of stem cell lines. Even more compelling is the possibility to directly reprogram a somatic cell into another adult cell type of a different tissue without the need for generating pluripotent cells. Here, I will discuss the immunological properties of mouse ES cell-derived hematopoietic progenitor cells. These progenitor cells poorly express MHC class I antigens but are responsive to stimulation by IFN-γ and other cytokines. However, despite upregulating MHC class I antigens after stimulation, they do not express class II molecules, a consequence of their lack of expression of the critical class II transcription factor CIITA. In this overview, I will discuss some of the published data on antigenicity and immunogenicity of ES cell-derived tissues. As more cells and tissues derived from ES cells become available for transplantation, we will gain more insight and into their abilities to interact with immune cells.