Macrophage overexpressing NGAL ameliorated kidney fibrosis in the UUO mice model

Background/Aims: Alternatively activated macrophages (AAM) have regenerative and anti-inflammatory characteristics. Here, we sought to evaluate whether AAM cell therapy reduces renal inflammation and fibrosis in the unilateral ureteral obstruction (UUO) mice model. Methods: We stabilized macrophages by adenoviral vector NGAL (Neutrophil gelatinase-associated lipocalin-2) and infused them into UUO mice. To ascertain whether macrophages were capable of reaching the obstructed kidney, macrophages were stained and detected by in vivo cell tracking. Results: We demonstrated that some infused macrophages reached the obstructed kidney and that infusion of macrophages overexpressing NGAL was associated with reduced kidney interstitial fibrosis and inflammation. This therapeutic effect was mainly associated with the phenotype and function preservation of the transferred macrophages isolated from the obstructed kidney Conclusions: Macrophage plasticity is a major hurdle for achieving macrophage therapy success in chronic nephropathies and could be overcome by transferring lipocalin-2

Macrophage overexpressing NGAL ameliorated kidney fibrosis in the UUO mice model

[Background/Aims] Alternatively activated macrophages (AAM) have regenerative and anti-inflammatory characteristics. Here, we sought to evaluate whether AAM cell therapy reduces renal inflammation and fibrosis in the unilateral ureteral obstruction (UUO) mice model.[Methods] We stabilized macrophages by adenoviral vector NGAL (Neutrophil gelatinase-associated lipocalin-2) and infused them into UUO mice. To ascertain whether macrophages were capable of reaching the obstructed kidney, macrophages were stained and detected by in vivo cell tracking.[Results] We demonstrated that some infused macrophages reached the obstructed kidney and that infusion of macrophages overexpressing NGAL was associated with reduced kidney interstitial fibrosis and inflammation. This therapeutic effect was mainly associated with the phenotype and function preservation of the transferred macrophages isolated from the obstructed kidney[Conclusions] Macrophage plasticity is a major hurdle for achieving macrophage therapy success in chronic nephropathies and could be overcome by transferring lipocalin-2.This research was supported by Spanish Government Instituto de Salud Carlos III (ISCIII) grant PI12/01427, PI15/00638 and PI12/00720 Confunded by FEDER funds/European Regional Development Fund (ERDF)-a way to Build Europe-//, 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).Peer reviewe