Human embryonic stem cells as a source of human mast cells for studies of allergies and inflammatory diseases

Abstract Human mast cells are principal cells initiating allergic reaction and asthma exacerbations. They are isolated either as mature cells from human tissues including skin and lung or differentiated from hematopoietic progenitors isolated from peripheral or cord blood. Isolation is accompanied with several disadvantages and difficulties including necessity of continuous access to human samples, low proliferation capacity and low efficiency in genetic modifications of isolated mast cells. In order to overcome these problems we developed a new strategy for differentiation of human mast cells from human embryonic stem (hES) cells. First, we differentiated hES cells to hematopoietic progenitors (CD34+ CD43+ cells) by co-culture of hES cells with stromal cells or by direct differentiation from embryonic bodies. Mast cells were subsequently differentiated in mast cell medium. Both approaches result in population of cells stained for mast cell specific proteins tryptase and chymase. They express a broad range of receptors and are able to be activated by their ligands. However, only mast cells differentiated directly from embryonic bodies express functional FcεRI. Together with techniques for genetic manipulation of hES cells, human ES cell-derived mast cells represent a unique model to analyze the effects of specific genetic alterations on human mast cell development, phenotype, and function.