Natural killer cell crosstalk with allogeneic human cardiac-derived stem/progenitor cells controls persistence

Cardiovasc Res. 2014 Nov 1;104(2):290-302. doi: 10.1093/cvr/cvu208. Epub 2014 Sep 11.


Aims: Allogeneic human cardiac-derived stem/progenitor cells (hCPC) are promising candidates for cardiac repair. They interact with T cells, major effectors of the adaptive immune response, inducing 'paracrine' anti-inflammatory effects that could sustain tissue repair/regeneration. Natural killer (NK) cells are major effectors of the innate immune system that might influence the persistence of therapeutic stem/progenitor cells. Therefore, to get through successful clinical translation and anticipate allogeneic hCPC persistence, we defined their crosstalk with NK cells under steady state and inflammatory conditions.

Methods and results: By using an experimental model of allogeneic hCPC/NK cell interaction, we demonstrate that hCPC moderately trigger cytokine-activated, but not resting, NK cell killing that occurs through formation of lytic immunological synapse and NK cell natural cytotoxicity. Yet, inflammatory context substantially decreases their capacity to set cytokine-activated NK cell functions towards NK cell-cytotoxicity and protects hCPC from NK cell killing. Allogeneic hCPC also restrain NK cell-cytotoxicity against conventional targets and inflammatory cytokine secretion biasing the latter towards anti-inflammatory cytokines. Thus, hCPC are unprivileged targets for allogeneic NK cells and can restrain NK cell functions in allogeneic setting.

Conclusion: Collectively, our data suggest that allogeneic hCPC/innate NK cells crosstalk within injured inflamed myocardium would permit their retention and might contribute to attenuating inflammation and to preventing adverse cardiac remodelling.

Keywords: Allogenicity; Human cardiac stem/progenitor cells; Myocardial infarction; NK cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Communication*
  • Cell Proliferation
  • Cells, Cultured
  • Coculture Techniques
  • Cytokines / immunology
  • Cytokines / metabolism
  • Cytotoxicity, Immunologic
  • Humans
  • Inflammation / immunology
  • Inflammation / metabolism*
  • Inflammation / pathology
  • Inflammation Mediators / immunology
  • Inflammation Mediators / metabolism
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism*
  • Lymphocyte Activation
  • Myocytes, Cardiac / immunology
  • Myocytes, Cardiac / metabolism*
  • Myocytes, Cardiac / pathology
  • Phenotype
  • Receptors, Immunologic / immunology
  • Receptors, Immunologic / metabolism
  • Signal Transduction
  • Stem Cells / immunology
  • Stem Cells / metabolism*


  • Cytokines
  • Inflammation Mediators
  • Receptors, Immunologic