Human pluripotent stem cells: a source of mast cells for the study of allergic and inflammatory diseases (86.16)

Abstract

Abstract Human mast cells are tissue resident cells with a principal role in allergic disorders. Cross-linking of the high-affinity receptor for IgE (FcϵRI) results in release of inflammatory mediators initiating the clinical symptoms of allergy and anaphylaxis. Much of our knowledge regarding the mechanisms of mast cell activation comes from studies of mouse bone marrow derived mast cells. However, clear differences have been identified between human and mouse mast cells. Studies of human mast cells are hampered by the limited sources available for their isolation, the resistance of these cells to genetic manipulation, and differences between cultures established from different individuals. To address this limitation, we developed a simple co-culture-free method for obtaining mast cells from human pluripotent stem cells (hPS) including human embryonic stem (hES) cells and induced pluripotent stem (iPS) cells. hES-derived mast cells respond to antigen by releasing mast cell mediators. Moreover, the cells can be generated in numbers sufficient for studies of the pathways involved in their effector functions. Genetically modified mast cells expressing GFP and Neo resistance were obtained by modification of hES cells prior to differentiation. iPS cells can be used for derivation of mast cells with patient specific genetic make-up. This direct co-culture-free differentiation of hPS cells represents a new and unique model to analyze the function and development of human mast cells.