Myeloid-derived suppressor cells generated from human induced pluripotent stem cells suppress T-cell proliferation 9306

Abstract Description Myeloid-derived suppressor cells (MDSCs) are myeloid cells with potent suppressive function. MDSC are generally associated with pathologies, and are otherwise rare, thereby restricting efforts to explore their biology. To address this limitation, we sought to generate and characterize MDSC-derived from human induced-pluripotent stem cells (iPSC). Embryoid bodies were used to facilitate generation of CD34+ hematopoietic progenitor cells from iPSC. CD34+ cells were further expanded and differentiated into CD45+CD33+HLA-DR- cells, MDSCs, in medium supplemented with GM-CSF and G-CSF or M-CSF. The predominant subsets of MDSCs, neutrophilic MDSCs (PMN-MDSCs, CD14-CD15+) and monocytic MDSCs (M-MDSCs, CD14+CD15-), were successfully generated in response to GM-CSF and G-CSF or M-CSF stimulation, respectively. Both MDSC populations suppressed proliferation of CD4+ and CD8+ T cells in vitro, dampening T cell secretion of GM-CSF, IL-6, IFN-γ, and TNF-α. Further planned characterization includes single cell RNA-seq, as well as more thorough quantification of MDSC subpopulation secretions and suppressive function. We anticipate that iPSC-derived MDSCs could be used as a tool to facilitate modeling of pathologies, such as tumor biology, or to assess medicines intended to target these cells. Topic Categories Technological Innovations in Immunology (TECH)