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Cited by 238Pluripotent Stem Cells ResearchHematopoietic Stem Cell TransplantationMesenchymal stem cell research

Large-scale hematopoietic differentiation of human induced pluripotent stem cells provides granulocytes or macrophages for cell replacement therapies

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Lachmann, Nico, Ackermann, Mania, Frenzel, Eileen, Liebhaber, Steffi, Brennig, Sebastian, Happle, Christine, Hoffmann, Dirk, Klimenkova, Olga +9 more·2015·Stem Cell Reports
DOI 10.1016/j.stemcr.2015.01.005PMC PMC4325194
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Abstract

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.

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  • iPSC-derived macrophages closely match tissue macrophages at both transcriptional and functional levels.

    “Importantly, these cells closely match tissue macrophages at both transcriptional and functional levels (184–186).”

    From Targeting macrophages in liver fibrosis (2026) · cites this paper as [184]

    The Results (Functional Characterization of M-CSF-Primed iPSC-MΦ) and Discussion report that iPSC-derived macrophages resemble peripheral-blood-derived macrophages in phagocytic activity and other functional measures. They do not establish a close transcriptional match or compare the cells with tissue macrophages; those parts of the claim are unsupported by this paper. (LLM, conf=0.88)

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Authors
Lachmann, N., Ackermann, M., Frenzel, E., Liebhaber, S., Brennig, S., Happle, C., Hoffmann, D., Klimenkova, O., Lüttge, D., Buchegger, T., Kühnel, M. P., Schambach, A., Janciauskiene, S., Figueiredo, C., Hansen, G., Skokowa, J., & Moritz, T.
Affiliations
  • Medizinische Hochschule Hannover (DE)
  • Boston Children's Hospital (US)
Corresponding author
Moritz, Thomas
ORCID
Venue
Stem Cell Reports
Publisher
Elsevier BV
Published
2015-02
Volume
4
Issue
2
Pages
282-296
ISSN
2213-6711 (ISSN-L)
DOI
10.1016/j.stemcr.2015.01.005
PMC
PMC4325194
OpenAlex
W2109570573
Cited by
238
References
53
Citations by year
2026: 15 · 2025: 14 · 2024: 38 · 2023: 20 · 2022: 19 · 2021: 32 · 2020: 26 · 2019: 21 · 2018: 17 · 2017: 24 · 2016: 7 · 2015: 5
FWCI
7.67
Type
journal article
Language
en
Open access
Licence
Locations
  • Stem Cell Reports (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • Deutsche Forschungsgemeinschaft (SFB-738, MO 886/6-1)
  • Bundesministerium für Bildung und Forschung
  • Medizinischen Hochschule Hannover (SFB738)
  • Deutsches Zentrum für Lungenforschung
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
  • Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
Keywords
induced pluripotent stem cells, hematopoietic differentiation, myeloid differentiation, interleukin-3, granulocyte colony-stimulating factor, macrophage colony-stimulating factor, granulocytes, macrophages, CD34+ cells, cell replacement therapy, neutrophil extracellular traps, phagocytosis, disease modeling
MeSH terms
Cell Differentiation, Granulocytes, Humans, Immunohistochemistry, Interleukin-3, Macrophages, Phenotype, Immunophenotyping, Granulocyte-Macrophage Colony-Stimulating Factor, Granulocyte Colony-Stimulating Factor, Cell Culture Techniques, Induced Pluripotent Stem Cells, Cell- and Tissue-Based Therapy

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