Exploring macrophage cell therapy on Diabetic Kidney Disease

Alternatively activated macrophages (M2) have regenerative properties and shown promise as cell therapy in chronic kidney disease. However, M2 plasticity is one of the major hurdles to overcome. Our previous studies showed that genetically modified macrophages stabilized by neutrophil gelatinase-associated lipocalin (NGAL) were able to preserve their M2 phenotype. Nowadays, little is known about M2 macrophage effects in diabetic kidney disease (DKD). The aim of the study was to investigate the therapeutic effect of both bone marrow-derived M2 (BM-phi M2) and phi-NGAL macrophages in the db/db mice. Seventeen-week-old mice with established DKD were divided into five treatment groups with their controls: D+BM-phi M2; D+phi-BM; D+phi-NGAL; D+phi-RAW; D+SHAM and non-diabetic (ND) (db/- and C57bl/6J) animals. We infused 1 x 10(6) macrophages twice, at baseline and 2 weeks thereafter. BM-phi M2 did not show any therapeutic effect whereas phi-NGAL significantly reduced albuminuria and renal fibrosis. The phi-NGAL therapy increased the anti-inflammatory IL-10 and reduced some pro-inflammatory cytokines, reduced the proportion of M1 glomerular macrophages and podocyte loss and was associated with a significant decrease of renal TGF-beta 1. Overall, our study provides evidence that phi-NGAL macrophage cell therapy has a therapeutic effect on DKD probably by modulation of the renal inflammatory response caused by the diabetic milieu.