Mesenchymal cell effect on the immune response in renovascular hypertension (INC1P.352)

Atherosclerotic renal artery sclerosis (RAS) is a significant public health concern, affecting 7% of the population over 65 years old and conveying an increased risk for cardiovascular as well as renal disease. Recent reports have failed to show a benefit of renal artery stenting to treat RAS. We tested the hypothesis that mesenchymal stem cells (MSC) slow the progression of renal injury by reducing inflammation. MSCs were isolated and cultured from murine adipocyte tissue and injected via the carotid artery into the animals 4 weeks after inducing RAS, a time at which the stenotic kidney has undergone severe atrophy. Conjugated microsphere labeling and flow cytometry confirmed that the MSCs migrate to the stenotic kidney. Half of the treatment group demonstrated a 90% reduction in atrophy and significantly lower level of regulatory T cell (Treg) infiltration while the other half demonstrated no change when compared to vehicle treated RAS mice. Array analysis showed a significant down-regulation of NOS2 (M1 macrophages), RORc (Th 17 cells), and CCR4 (associated with M1 macrophages) within those mice with low renal atrophy. The results suggest that under certain conditions, MSCs have a possible effect on the inflammatory environment present in RAS mice. Future studies will determine whether intervention prior to development of severe atrophy will increase therapeutic efficacy of MSC.