ArticleBlood advances2018
NK cell development in a human stem cell niche: KIR expression occurs independently of the presence of HLA class I ligands.
Article in Blood advances, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- Cellular immunotherapy in melanoma: the next frontier in cancer treatment.Journal of experimental & clinical cancer research : CR · 2026Review
- Differentiation of cord blood-derived Innate Lymphoid Cells 1 into KIR+NKG2A- natural killer cells in a human stem cell niche.Stem cells translational medicine · 2026Article
- Progress in cell-based immunotherapies for solid tumors.Discover oncology · 2026Review
- Serum-free differentiation platform for the generation of B lymphocytes and natural killer cells from human CD34+ cord blood progenitors.Scientific reports · 2025Article
- A human NK cell progenitor that originates in the thymus and generates KIRScience advances · 2025Article
- CAR-NK cells derived from cord blood originate mainly from CD56Molecular therapy. Methods & clinical development · 2024Article
- Review
- Quantifying Human Natural Killer Cell Migration by Imaging and Image Analysis.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Detailed phenotypic and functional characterization of CMV-associated adaptive NK cells in rhesus macaques.Frontiers in immunology · 2022Article
- Natural Killer Cells Generated From Human Induced Pluripotent Stem Cells Mature to CD56Frontiers in immunology · 2021Article
- EfficientFrontiers in immunology · 2021Article
- Generation of cell-derived matrices that support human NK cell migration and differentiation.Journal of leukocyte biology · 2020Article
- Article
- Umbilical cord blood-derived ILC1-like cells constitute a novel precursor for mature KIReLife · 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
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The development of mature natural killer (NK) cells expressing killer cell immunoglobulin-like receptors (KIRs) depends on cell contact-dependent signals from nonhematopoietic cells. So far, detailed studies of this process have been hampered by the lack of an appropriate in vitro model. Here, human bone marrow-derived mesenchymal stem cells (MSCs), generated under good manufacturing practice (GMP) conditions, are established as a supportive niche for in vitro NK cell differentiation. In the presence of MSCs, cord blood and bone marrow-derived hematopoietic stem and progenitor cells (HSPCs) effectively and reproducibly differentiated into mature KIR-expressing NK cells. Notably, the novel in vitro differentiation assay enabled us to analyze the impact of HLA class I ligands on KIR repertoire development. To this end, a panel of MSC lines divergent for expression of the major KIR ligands C1, C2, and Bw4 was used for NK cell differentiation. The resulting NK cell repertoires were independent of the presence of specific KIR ligands on MSCs and were, in fact, invariably dominated by expression of the C1-specific inhibitory KIR2DL3. Similarly, short hairpin RNA-mediated knockdown of HLA class I ligands on MSCs did not delay or change the course of KIR expression. Our data suggest that the initial acquisition of KIRs during NK cell development is biased toward recognition of C1 ligands, irrespective of the presence of self-ligands. Altogether, the MSC/HSPC model constitutes a novel platform to study NK cell development in a human stem cell niche. Moreover, the system constitutes a promising GMP-compliant platform to develop clinical-grade NK cell products from cord blood HSPCs.
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