, Volume 71, Issue 1, pp 375–388 | Cite as

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

  • Mehdi Najar
  • Mohammad Fayyad-KazanEmail author
  • Makram Merimi
  • Nathalie Meuleman
  • Dominique Bron
  • Hussein Fayyad-Kazan
  • Laurence Lagneaux
Original Article


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.


AT-MSCs NK cells Immunomodulation Cell crosstalk 



Adipose tissue


Tumor necrosis factor








Mesenchymal stromal cells


Natural killer


Peripheral blood mononuclear cells


Reactive oxygen species



We thank Karlien Pieters for her technical assistance.


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

Compliance with ethical standards

Conflicts of interest

The authors declare that there is no conflict of interest regarding the publication of this article.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the ethics committee of the “Institut Jules Bordet” (Belgium) and with the 1964 Helsinki declaration and its later amendments.

Informed consent

Informed consent was obtained from all individual participants included in the study.


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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  • Mehdi Najar
    • 1
    • 2
  • Mohammad Fayyad-Kazan
    • 3
    Email author
  • Makram Merimi
    • 3
    • 4
  • Nathalie Meuleman
    • 1
    • 3
  • Dominique Bron
    • 1
    • 3
  • Hussein Fayyad-Kazan
    • 5
  • Laurence Lagneaux
    • 1
  1. 1.Laboratory of Clinical Cell Therapy, Institut Jules BordetUniversité Libre de Bruxelles (ULB)BrusselsBelgium
  2. 2.Osteoarthritis Research UnitUniversity of Montreal Hospital Research Center (CRCHUM)MontrealCanada
  3. 3.Hematology Department, Institut Jules BordetUniversité Libre de BruxellesBrusselsBelgium
  4. 4.Laboratory of Physiology, Genetics and Ethnopharmacology, Faculty of SciencesUniversity Mohammed PremierOujdaMorocco
  5. 5.Laboratory of Cancer Biology and Molecular Immunology, Faculty of Sciences ILebanese UniversityHadathLebanon

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