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Keeping Neutrophils Under Control with MSCs!

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Review of “Suppression of Neutrophil-Mediated Tissue Damage – A Novel Skill of Mesenchymal Stem Cells” from Stem Cells by Stuart P. Atkinson

The activation of neutrophils is a potent and effective immune response to the threat of microorganism invasion of the human body. However, the aberrant activation of neutrophils associated with certain disorders or in reaction to trauma and chronic non-healing wounds [1] can cause severe damage and tissue breakdown.

We also lack effective treatment strategies and this led researchers from the laboratory of Karin Scharffetter-Kochanek (University of Ulm, Germany) to investigate if the anti-inflammatory capacities of mesenchymal stem cells (MSCs) [2] could represent a potential solution. Their new findings, reported in Stem Cells, suggest that a stem cell-based therapeutic approach may hold great potential [3].

Initial studies first assessed the effect of MSCs on neutrophil oxidative burst, the rapid release of reactive oxygen species normally employed to destroy microorganisms. Interestingly, the application of human adipose tissue-derived MSCs inhibited oxidative burst in neutrophils in vitro and in vivo in a mouse dermatitis model [4] and correlated to a decrease in neutrophil death. Furthermore, MSC injection also reduced neutrophil recruitment and protected vessel structure in a mouse model of immune complex-mediated vasculitis in which activated neutrophils normally damage vessel walls resulting in edema and hemorrhage.

But just how are MSCs preventing all this neutrophil-mediated tissue damage?? The study highlighted four main strategies (See Figure); 1) suppressing the formation of neutrophil extracellular traps (NETs), used to trap and kill microorganisms [5], 2) engulfing and neutralizing neutrophils, 3) inhibiting the spillage of extracellular matrix-degrading enzymes, and 4) the constitutive release of superoxide dismutase 3 (SOD3) to inhibit the consequences of  reactive oxygen species release [6]. 

High levels of morbidity and mortality are normally associated with the damage caused by unwanted neutrophil activation, although this study may now describe a potentially exciting means to inhibit such consequences. MSCs seems to have a potent ability to keep those pesky neutrophils under control, but will this treatment strategy move from the bench to the bedside? Keep tuned to the Stem Cells Portal to find out!

References

  1. McDaniel JC, Roy S, and Wilgus TA. Neutrophil activity in chronic venous leg ulcers--a target for therapy? Wound Repair Regen 2013;21:339-351.
  2. Stappenbeck TS and Miyoshi H. The role of stromal stem cells in tissue regeneration and wound repair. Science 2009;324:1666-1669.
  3. Jiang D, Muschhammer J, Qi Y, et al. Suppression of Neutrophil-Mediated Tissue Damage-A Novel Skill of Mesenchymal Stem Cells. Stem Cells 2016;34:2393-2406.
  4. Fretland DJ, Gokhale R, Mathur L, et al. Dermal inflammation in primates, mice, and guinea pigs: attenuation by second-generation leukotriene B4 receptor antagonist, SC-53228. Inflammation 1995;19:333-346.
  5. Brinkmann V, Reichard U, Goosmann C, et al. Neutrophil extracellular traps kill bacteria. Science 2004;303:1532-1535.
  6. Kemp K, Gray E, Mallam E, et al. Inflammatory cytokine induced regulation of superoxide dismutase 3 expression by human mesenchymal stem cells. Stem Cell Rev 2010;6:548-559.