Large-scale hematopoietic differentiation of human induced pluripotent stem cells provides granulocytes or macrophages for cell replacement therapies.
Large-scale hematopoietic differentiation of human induced pluripotent stem cells provides granulocytes or macrophages for cell replacement therapies.
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DOI:
10.1016/j.stemcr.2015.01.005
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发表时间:
2015-02-10
影响因子:
5.9
通讯作者:
Moritz T
中科院分区:
文献类型:
--
作者:
Lachmann N;Ackermann M;Frenzel E;Liebhaber S;Brennig S;Happle C;Hoffmann D;Klimenkova O;Lüttge D;Buchegger T;Kühnel MP;Schambach A;Janciauskiene S;Figueiredo C;Hansen G;Skokowa J;Moritz T
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. Myeloid specification of human PSCs by IL-3-/M-CSF, G-CSF, or GM-CSF Large-scale and continuous generation of M2-MΦ or granulocytes by M-CSF or G-CSF Functional iPSC-derived macrophages or granulocytes similar to in-vivo-derived cells In this article, Moritz and colleagues show that IL-3 in combination with M-CSF/G-CSF or GM-CSF is able to instruct human pluripotent stem cells toward a myeloid lineage. The use of IL-3/G-CSF or IL-3/M-CSF allows for prolonged and large-scale production of human granulocytes or macrophages, respectively, that demonstrate similar functionalities compared with their in-vivo-derived counterparts.
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影响因子:
2.7
作者:
EVANS, WH;WILSON, SM;MAGE, MG
通讯作者:
MAGE, MG
影响因子:
56.9
作者:
CLARK, SC;KAMEN, R
通讯作者:
KAMEN, R
DOI:
10.1084/jem.20131199
发表时间:
2013-09-23
期刊:
The Journal of experimental medicine
影响因子:
--
作者:
Guilliams M;De Kleer I;Henri S;Post S;Vanhoutte L;De Prijck S;Deswarte K;Malissen B;Hammad H;Lambrecht BN
通讯作者:
Lambrecht BN
影响因子:
21.3
作者:
通讯作者:
--
影响因子:
4.4
作者:
Lacey, Derek C.;Achuthan, Adrian;Hamilton, John A.
通讯作者:
Hamilton, John A.