Mesenchymal stem cells (MSCs) are being widely studied for their ability to regulate macrophage cell responses. Previous works have demonstrated that mouse aorta-derived MSC (mAo-MSC) support the macrophage inflammatory response. mAo-MSC have been characterized phenotypically for MSC-associated surface antigens and express CD90 and CD105 but do not express CD73. CD105, also known as endoglin, is a coreceptor in the TGFβ superfamily of receptors. Mouse adipose-derived MSC lacking CD105 have an increased capacity to regulate T-cells by reducing their proliferation while elevated CD105 expression is consistently associated with inflammatory disease. Therefore, we hypothesized that suppression of CD105 in mAo-MSC will reduce the immunosupportive capacity of the mAo-MSC. We used siRNA to reduce expression of CD105 in mAo- MSC and subsequently examined the effect of this deficiency on their response to lipopolysaccharide (LPS) and their ability to support the macrophage inflammatory response. Contrary to our hypothesis, CD105 deficient mAo-MSC cultured alone and in co-culture with macrophage secreted increased levels of the inflammatory indicators nitric oxide (NO) and interleukin 6 (IL-6) after exposure to LPS. The increase in NO and IL-6 observed in the co-cultures is additive and therefore points to the mAo- MSC as the primary origin. Overall our data suggest that CD105 acts as a regulator of the TLR-4 pathway and may represent an important target for modification of MSC to be used in therapeutics.
Available at: http://works.bepress.com/jodi-evans/5/