Fetal and adult multipotent mesenchymal stromal cells are killed by different pathways

Cytotherapy. 2011 Mar;13(3):269-78. doi: 10.3109/14653249.2010.523077. Epub 2010 Oct 14.


Background aims: Multipotent mesenchymal stromal cells, also known as mesenchymal stem cells (MSC), can be isolated from adult and fetal tissues. Recently, there has been considerable interest in MSC because they have features favorable for transplantation, namely their multipotency and non-immunogenic properties.

Methods: We analyzed how human MSC derived from first-trimester fetal liver and adult bone marrow interact with naive and activated innate natural killer (NK) cells. NK cell function was studied by measuring killing of MSC, as well as degranulation (CD107a) induced by MSC. To assess the importance of NK cell killing, expression of surface epitopes was analyzed by flow cytometry on MSC before and after stimulation with interferon (IFN)γ.

Results: Fetal and adult MSC express several ligands to activating NK cell receptors as well as low levels of HLA class I, with large inter-individual variation. Naive peripheral blood NK cells did not lyse fetal or adult MSC, whereas interleukin (IL)2 activated allogeneic as well as autologous NK cells did. Pre-incubation of MSC with IFN-γ increased their levels of HLA class I, protecting them from NK cell recognition. Fetal and adult MSC were preferably killed via the tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and Fas ligand (FasL) pathways, respectively. Blocking NKG2D reduced NK cell degranulation in both fetal and adult MSC.

Conclusions: Fetal and adult MSC differ in their interactions with NK cells. Both fetal and adult MSC are susceptible to lysis by activated NK cells, which may have implications for the use of MSC in cell therapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Adult Stem Cells / cytology*
  • Adult Stem Cells / immunology
  • Aged
  • Cell Death / drug effects
  • Child
  • Child, Preschool
  • Fas Ligand Protein / pharmacology
  • Fetus / cytology*
  • Fetus / immunology
  • Humans
  • Interferon-gamma / pharmacology
  • Interleukin-2 / pharmacology
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism
  • Ligands
  • Lymphocyte Activation / drug effects
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / immunology
  • Mesenchymal Stem Cells / metabolism
  • Middle Aged
  • Multipotent Stem Cells / cytology*
  • Multipotent Stem Cells / drug effects
  • Multipotent Stem Cells / immunology
  • Multipotent Stem Cells / metabolism
  • Signal Transduction / drug effects
  • Stromal Cells / cytology
  • Stromal Cells / drug effects
  • Stromal Cells / immunology
  • Stromal Cells / metabolism
  • TNF-Related Apoptosis-Inducing Ligand / pharmacology
  • Young Adult


  • Fas Ligand Protein
  • Interleukin-2
  • Ligands
  • TNF-Related Apoptosis-Inducing Ligand
  • Interferon-gamma