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Large-Scale Hematopoietic Differentiation of Human Induced Pluripotent Stem Cells Provides Granulocytes or Macrophages for Cell Replacement Therapies
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-cel...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4325194/ https://www.ncbi.nlm.nih.gov/pubmed/25680479 http://dx.doi.org/10.1016/j.stemcr.2015.01.005 |
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author | Lachmann, Nico Ackermann, Mania Frenzel, Eileen Liebhaber, Steffi Brennig, Sebastian Happle, Christine Hoffmann, Dirk Klimenkova, Olga Lüttge, Doreen Buchegger, Theresa Kühnel, Mark Philipp Schambach, Axel Janciauskiene, Sabina Figueiredo, Constanca Hansen, Gesine Skokowa, Julia Moritz, Thomas |
author_facet | Lachmann, Nico Ackermann, Mania Frenzel, Eileen Liebhaber, Steffi Brennig, Sebastian Happle, Christine Hoffmann, Dirk Klimenkova, Olga Lüttge, Doreen Buchegger, Theresa Kühnel, Mark Philipp Schambach, Axel Janciauskiene, Sabina Figueiredo, Constanca Hansen, Gesine Skokowa, Julia Moritz, Thomas |
author_sort | Lachmann, Nico |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4325194 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-43251942015-02-14 Large-Scale Hematopoietic Differentiation of Human Induced Pluripotent Stem Cells Provides Granulocytes or Macrophages for Cell Replacement Therapies Lachmann, Nico Ackermann, Mania Frenzel, Eileen Liebhaber, Steffi Brennig, Sebastian Happle, Christine Hoffmann, Dirk Klimenkova, Olga Lüttge, Doreen Buchegger, Theresa Kühnel, Mark Philipp Schambach, Axel Janciauskiene, Sabina Figueiredo, Constanca Hansen, Gesine Skokowa, Julia Moritz, Thomas Stem Cell Reports Resource 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. Elsevier 2015-02-10 /pmc/articles/PMC4325194/ /pubmed/25680479 http://dx.doi.org/10.1016/j.stemcr.2015.01.005 Text en © 2015 The Authors http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/). |
spellingShingle | Resource Lachmann, Nico Ackermann, Mania Frenzel, Eileen Liebhaber, Steffi Brennig, Sebastian Happle, Christine Hoffmann, Dirk Klimenkova, Olga Lüttge, Doreen Buchegger, Theresa Kühnel, Mark Philipp Schambach, Axel Janciauskiene, Sabina Figueiredo, Constanca Hansen, Gesine Skokowa, Julia Moritz, Thomas Large-Scale Hematopoietic Differentiation of Human Induced Pluripotent Stem Cells Provides Granulocytes or Macrophages for Cell Replacement Therapies |
title | Large-Scale Hematopoietic Differentiation of Human Induced Pluripotent Stem Cells Provides Granulocytes or Macrophages for Cell Replacement Therapies |
title_full | Large-Scale Hematopoietic Differentiation of Human Induced Pluripotent Stem Cells Provides Granulocytes or Macrophages for Cell Replacement Therapies |
title_fullStr | Large-Scale Hematopoietic Differentiation of Human Induced Pluripotent Stem Cells Provides Granulocytes or Macrophages for Cell Replacement Therapies |
title_full_unstemmed | Large-Scale Hematopoietic Differentiation of Human Induced Pluripotent Stem Cells Provides Granulocytes or Macrophages for Cell Replacement Therapies |
title_short | Large-Scale Hematopoietic Differentiation of Human Induced Pluripotent Stem Cells Provides Granulocytes or Macrophages for Cell Replacement Therapies |
title_sort | large-scale hematopoietic differentiation of human induced pluripotent stem cells provides granulocytes or macrophages for cell replacement therapies |
topic | Resource |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4325194/ https://www.ncbi.nlm.nih.gov/pubmed/25680479 http://dx.doi.org/10.1016/j.stemcr.2015.01.005 |
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