This entry is in regards to an interesting review article in the October, 2013 Stem Cells journal, by Darwin J. Prockop, M.D., Ph.D from Texas A&M University. He writes about two specific negative feedback loops that stem cells introduce into generic pathways of inflammation.
(I apologize about the technical aspect of this blog entry, but I found it difficult to put a lot of the medical terminology into layperson terms.)
The first feedback loop is brought about by pro-inflammatory mediators from certain sensor cells that activate stem cells and upregulate the expression of COX2 and other parts of the arachidonic acid pathway. This then causes the stem cells to secrete more prostaglandin E2 (PGE2) which then appears to cause pro-inflammatory macrophages to instead secrete anti-inflammatory mediators (including interleukin-10 and interleukin-1).
The second negative feedback loop also involves stem cell activation from mediators. This activation causes stem cells to increase the expression of certain genes, specifically the anti-inflammatory protein TNF-alpha stimulated gene/protein 6 (TSG-6). This results in a decrease in TNF-alpha and other mediators that stimulate inflammation.
These two loops provide evidence that stem cells have a definite effect in decreasing inflammation, a finding that once again shows promise for stem cells as a treatment modality.
The lab testing evidence for these two loops was developed primarily in experiments wherein the stem cells were given after an acute tissue injury that induced the inflammatory response. The author notes that further investigation is needed to determine if these feedback loops exist in situations such as mild inflammation or unresolved inflammation due to a chronic disease process. It is also intriguing to note if these negative feedback loops would exist in all patients, or if genetic differences would influence them.
These negative feedback loops are only one portion of the role that stem cells have in the healing response. There are many other factors involved, including stimulation of growth factors, increased vascularization, recruitment of more host stem cells, modulation of the immune response, reduction of reactive oxygen species, transdifferentiation of cell types, and increased paracrine signaling, among many other methods.
