Chronic Inflammation Inhibits Endogenous Neural Stem Cells

Valencia, Spain -

Mesenchymal stem cells are widely known to possess anti-inflammatory and immune modulatory activity.  The regenerative and trophic functions of this type of stem cell may actually be less important than their ability to block pathological cytokine expression.  In fact, the first non-hematopoietic stem cell product that will likely be approved by the FDA appears to be bone marrow derived mesenchymal stem cells for treatment of the inflammatory conditions Crohn's Disease and Graft Versus Host.

Why are mesenchymal stem cells so immune suppressive?

One possible explanation would be that the mesenchymal stem cells serve to protect the hematopoietic stem cells from inflammatory insults.  It is known that even small degree of bone marrow inflammation may have disasterous consequences on the tightly-controlled network that regulates orderly production of blood cells.  If this is the case, one would ask, do inflammatory conditions effect other types of stem cells?  

We know on the one hand that acute inflammation, such as a heart attack or stroke causes mobilization of stem cells.  But what is the impact of a chronic inflammatory state on the tissue specific stem cells in the inflammed tissue?   This question was examined in a recent study (Pluchino et al. Persistent inflammation alters the function of the endogenous brain stem cell compartment. Brain 2008 Aug 30). 

The scientists induced a myelin-specific immune response (similar to multiple sclerosis) as a model of chronic neural inflammation, and assessed proliferation of endogenous neural stem cells in the subventricular zone.  A profound decrease in proliferative activity of the endogenous stem cells was observed in the animals suffering chronic inflammation as compared to controls.

These data extent the previous findings that hematopoietic stem cells are inhibited by inflammation to neural stem cells.  Given that agents such as PACAP and Prolactin are known to activate proliferation of endogenous stem cells in the brain, it will be interesting to see how these agents will be applied to various degenerative diseases associated with chronic inflammation.