ArticleExperimental hematology2008
Mouse fetal and embryonic liver cells differentiate human umbilical cord blood progenitors into CD56-negative natural killer cell precursors in the absence of interleukin-15.
Article in Experimental hematology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 45 citations in OpenAlex.
- Article
- CXCR4 coordinates adhesion, migration, and development of human NK cells.bioRxiv : the preprint server for biology · 2026Article
- Serum-free differentiation platform for the generation of B lymphocytes and natural killer cells from human CD34+ cord blood progenitors.Scientific reports · 2025Article
- Cytokines in Focus: IL-2 and IL-15 in NK Adoptive Cell Cancer Immunotherapy.Immune network · 2025Review
- Unwinding the Role of the CMG Helicase in Inborn Errors of Immunity.Journal of clinical immunology · 2023Article
- In Vitro Development of Mouse and Human NK Cells from Hematopoietic Progenitor Cells.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Stem cells-derived natural killer cells for cancer immunotherapy: current protocols, feasibility, and benefits of ex vivo generated natural killer cells in treatment of advanced solid tumors.Cancer immunology, immunotherapy : CII · 2021Review
- Article
- Transcription Factors Associated With IL-15 Cytokine Signaling During NK Cell Development.Frontiers in immunology · 2021Review
- Generation of cell-derived matrices that support human NK cell migration and differentiation.Journal of leukocyte biology · 2020Article
- Human NK cell deficiency as a result of biallelic mutations in MCM10.The Journal of clinical investigation · 2020Article
- From stem cell to immune effector: how adhesion, migration, and polarity shape T-cell and natural killer cell lymphocyte development in vitro and in vivo.Molecular biology of the cell · 2020Review
- HCMV Infection in a Mesenchymal Stem Cell Niche: Differential Impact on the Development of NK Cells versus ILC3.Journal of clinical medicine · 2019Article
- Emerging insights into human health and NK cell biology from the study of NK cell deficiencies.Immunological reviews · 2019Review
- NK cell development in a human stem cell niche: KIR expression occurs independently of the presence of HLA class I ligands.Blood advances · 2018Article
- Generation of "Off-the-Shelf" Natural Killer Cells from Peripheral Blood Cell-Derived Induced Pluripotent Stem Cells.Stem cell reports · 2017Article
- OP9 Feeder Cells Are Superior to M2-10B4 Cells for the Generation of Mature and Functional Natural Killer Cells from Umbilical Cord Hematopoietic Progenitors.Frontiers in immunology · 2017Article
- Human NK cell development requires CD56-mediated motility and formation of the developmental synapse.Nature communications · 2016Article
- Silent IL2RG Gene Editing in Human Pluripotent Stem Cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Article
- Cord Blood as a Source of Natural Killer Cells.Frontiers in medicine · 2015Review
Corrections and comments
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Authors and funding
7 authors at 6 institutions in 3 countries.
Funding
Abstract
objectiveHuman natural killer (NK) cell maturation involves the orderly acquisition of NK cell receptors. Our aim was to understand how stromal interactions and cytokines are important in this developmental process. MATERIALS AND
methodsHuman umbilical cord blood (UCB) CD34(+)/Lin(-)/CD38(-) cells were cultured on two murine stromal cell lines (AFT024 and EL08-1D2) in a switch culture to study NK cell development.
resultsWhen human progenitors were cultured on AFT024 with interleukin (IL)-3 and Flt3 ligand (Flt3L) in the absence of interleukin (IL)-15, NK cell differentiation occurred, albeit at low frequency. These conditions favored the accumulation of CD56(-) NK cell precursors (CD34(+)CD7(-), CD34(+)CD7(+), and CD34(-)CD7(+) cells), which are populations rare in adult blood but abundant in fresh UCB. In secondary culture, addition of IL-3 or IL-3 + Flt3L to IL-15 increased the absolute number of CD56(+) NK cells from precursors and the acquisition of CD94 and killer immunoglobulin-like receptors (KIR). To further explore the microenvironment in early NK cell maturation, a cell line derived from murine embryonic liver (EL08-1D2) was studied. NK cell development and KIR acquisition was superior with EL08-1D2, which supported the differentiation of NK cell precursors, NK cell commitment, and proliferation.
conclusionAlthough the earliest events in NK cell maturation do not require exogenous human IL-15, it is required at a later stage of NK cell commitment. At a minimum, murine stroma, IL-3, and Flt3L are required to recapitulate early NK cell development and differentiation into distinct NK cell precursors. EL08-1D2 induces KIR acquisition suggesting that extrinsic signals in NK cell development are conserved between mouse and man.
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