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-фM2) and ф-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-фM2; D+ф-BM; D+ф-NGAL; D+ф-RAW; D+SHAM and non-diabetic (ND) (db/- and C57bl/6J) animals. We infused 1 × 10 macrophages twice, at baseline and 2 weeks thereafter. BM-фM2 did not show any therapeutic effect whereas ф-NGAL significantly reduced albuminuria and renal fibrosis. The ф-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-β1. Overall, our study provides evidence that ф-NGAL macrophage cell therapy has a therapeutic effect on DKD probably by modulation of the renal inflammatory response caused by the diabetic milieu.
This work was supported by Spanish Government Instituto de Salud Carlos III (ISCIII) grant PI12/01427, PI15/00638 and PI12/ 00720, AMGEN grant under the auspices of The Red de Investigación Renal (European Regional Development Funds ISCIII Red Temática de Investigación Cooperativa en Salud Red de Investigación Renal; RD16/0009/0003) and SENEFRO (awarded to AS). SAF 2015‐ 67770 (awarded to GH). AS is supported by Miguel Servet Contracting System (CP08/00138).