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Reciprocal immuno-biological alterations occur during the co-culture of natural killer cells and adipose tissue-derived mesenchymal stromal cells

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Abstract

Due to their immune-therapeutic value, adipose tissue-derived mesenchymal stromal cells (AT-MSCs) require a better characterization of their interplay with natural killer (NK) cells known to contribute to the graft-versus-leukemia effects. When cultivated together, AT-MSCs showed cellular cytotoxicity and were therefore killed by NK cells in an activating-cytokine dependent manner. In the presence of AT-MSCs, both ligands and receptors known to drive NK cell interactions were significantly altered. During this co-culture, the proliferation of NK cells was slightly reduced, while their IFN-γ and TNF-α secretion was significantly increased. NK cells displayed sustained degranulation accompanied by increased discharge of their cytolytic granules (perforin, granzymes A and B). On the other hand, activated NK cells reduced the expression of serpins C1 and B9 in AT-MSCs. Collectively, reciprocal immuno-biological alterations occur during the co-culture of NK cells and AT-MSCs. Understanding these changes will increase the safety and efficacy of cell-based immuno-oncotherapy.

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Abbreviations

AT:

Adipose tissue

TNF:

Tumor necrosis factor

GVL:

Graft-versus-leukemia

GVH:

Graft-versus-host

IFN:

Interferon

MSCs:

Mesenchymal stromal cells

NK:

Natural killer

PBMCs:

Peripheral blood mononuclear cells

ROS:

Reactive oxygen species

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Acknowledgements

We thank Karlien Pieters for her technical assistance.

Funding

This project was supported by “Le Fonds National de la Recherche Scientifique, F.R.S.-FNRS” and the “Télévie”.

Author information

Author notes

  1. Mehdi Najar and Mohammad Fayyad-Kazan are co-first authors with equal contribution.

  2. Hussein Fayyad-Kazan and Laurence Lagneaux are senior co-authors.

Authors and Affiliations

  1. Laboratory of Clinical Cell Therapy, Institut Jules Bordet, Université Libre de Bruxelles (ULB), Campus Erasme, Brussels, Belgium

    Mehdi Najar, Nathalie Meuleman, Dominique Bron & Laurence Lagneaux

  2. Osteoarthritis Research Unit, University of Montreal Hospital Research Center (CRCHUM), 900 Saint-Denis, R11.424, Montreal, QC, H2X 0A9, Canada

    Mehdi Najar

  3. Hematology Department, Institut Jules Bordet, Université Libre de Bruxelles, 121 Boulevard de Waterloo, 1000, Brussels, Belgium

    Mohammad Fayyad-Kazan, Makram Merimi, Nathalie Meuleman & Dominique Bron

  4. Laboratory of Physiology, Genetics and Ethnopharmacology, Faculty of Sciences, University Mohammed Premier, Oujda, Morocco

    Makram Merimi

  5. Laboratory of Cancer Biology and Molecular Immunology, Faculty of Sciences I, Lebanese University, Hadath, Lebanon

    Hussein Fayyad-Kazan

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Correspondence to Mohammad Fayyad-Kazan.

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Najar, M., Fayyad-Kazan, M., Merimi, M. et al. Reciprocal immuno-biological alterations occur during the co-culture of natural killer cells and adipose tissue-derived mesenchymal stromal cells. Cytotechnology 71, 375–388 (2019). https://doi.org/10.1007/s10616-019-00294-6

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  • DOI: https://doi.org/10.1007/s10616-019-00294-6

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