TLRs and Stem Cell Mobilization

Cornell University, New York City, New York -

We have discussed on StemCellPatents.com how various inflammatory stimuli may one the one hand act as stem cell chemo-attractants, and on the other hand may actually cause mobilization of stem cells to leave the bone marrow.  For example, injured tissue is associated with platelet activation, causing release of agents such as sphingosine-1-phosphate, which then acts to attract stem cells.  On the other hand, events such as a cardiac infarct, or a stroke, or even viral (coxsackie) infection of the myocardium, are associated with mass release of cytokines like VEGF or SDF-1 which not only chemo-attract stem cells but also are involved in their mobilization and exit from the bone marrow compartment.  If inflammation is associated with stem cell homing, then it would make sense that the receptors responsible for recognizing tissue damage, for example toll like receptors, should be involved in stem cell homing.  While it has been reported that ligation of TLR3 and/or TLR4 on mesenchymal stem cells can inactivate their immune suppressive properties, the role of toll like receptors in the homing of stem cells has not been elucidated.

In a recent study (Kuo et al. Ischemia-Induced Exocytosis of Weibel-Palade Bodies Mobilizes Stem Cells. J Am Soc Nephrol. 2008 Aug 20.) a very interesting link was made between TLRs and stem cell mobilization.  The authors demonstrated that monosodium urate (which is found in high concentrations in ischemic tissues) induces systemic release of Weibel-Palade bodies, these Weibel-Palade bodies then go on to induce upregulation of IL-8, vW Factor, and the cytokine angiopoietin 2. 

When animals lacking TLR-2/4 were treated with uric acid, no mobilization of stem cells was seen.  This suggests that the uric acid may induce mobilization, directly or indirectly through activation of a TLR pathway.