Lachmann, NicoAckermann, ManiaFrenzel, EileenLiebhaber, SteffiBrennig, SebastianHapple, ChristineHoffmann, DirkKlimenkova, OlgaLüttge, DoreenBuchegger, TheresaKühnel, Mark PhilippSchambach, AxelJanciauskiene, SabinaFigueiredo, ConstancaHansen, GesineSkokowa, JuliaMoritz, Thomas2015-03-022015Lachmann, N., M. Ackermann, E. Frenzel, S. Liebhaber, S. Brennig, C. Happle, D. Hoffmann, et al. 2015. “Large-Scale Hematopoietic Differentiation of Human Induced Pluripotent Stem Cells Provides Granulocytes or Macrophages for Cell Replacement Therapies.” Stem Cell Reports 4 (2): 282-296. doi:10.1016/j.stemcr.2015.01.005. http://dx.doi.org/10.1016/j.stemcr.2015.01.005.2213-6711http://nrs.harvard.edu/urn-3:HUL.InstRepos:14065550Summary Interleukin-3 (IL-3) is capable of supporting the proliferation of a broad range of hematopoietic cell types, whereas granulocyte colony-stimulating factor (G-CSF) and macrophage CSF (M-CSF) represent critical cytokines in myeloid differentiation. When this was investigated in a pluripotent-stem-cell-based hematopoietic differentiation model, IL-3/G-CSF or IL-3/M-CSF exposure resulted in the continuous generation of myeloid cells from an intermediate myeloid-cell-forming complex containing CD34+ clonogenic progenitor cells for more than 2 months. Whereas IL-3/G-CSF directed differentiation toward CD45+CD11b+CD15+CD16+CD66b+ granulocytic cells of various differentiation stages up to a segmented morphology displaying the capacity of cytokine-directed migration, respiratory burst response, and neutrophil-extracellular-trap formation, exposure to IL-3/M-CSF resulted in CD45+CD11b+CD14+CD163+CD68+ monocyte/macrophage-type cells capable of phagocytosis and cytokine secretion. Hence, we show here that myeloid specification of human pluripotent stem cells by IL-3/G-CSF or IL-3/M-CSF allows for prolonged and large-scale production of myeloid cells, and thus is suited for cell-fate and disease-modeling studies as well as gene- and cell-therapy applications.en-USJournal Article2015-03-0210.1016/j.stemcr.2015.01.005