FP293BONE MARROW M2 MACROPHAGE CELL THERAPY DOES NOT INDUCE RENOPROTECTION IN UUO MICE MODEL

Abstract

Introduction and Aims: Alternatively activated macrophages (M2) have regenerative properties and shown promise as a potential cellular therapeutic strategy for acute and chronic kidney disease. The aim of this study was to evaluate whether bone marrow-derived M2 macrophages (BM-M2) cell therapy could induce tissue repair in the UUO mice model of chronic kidney damage. Methods: UUO surgery was performed on 8 week-old C57BL6J male mice. At day 7 after surgery, 1x106cells/animal were injected via the tail vein. Transfused macrophages were examined by immunofluorescence staining and in vivo tracking. Mice were killed and evaluated on day 9 and day 15 after UUO surgery, and divided into five groups: wild type (n=4); UUO-d9, killed at day 9 (n=9); UUO-d15, killed at day 15 (n=9), UUO +BM-M2-d9, animals with BM-M2 macrophage infusion and killed at day 9 (n=9); UUO +BM-M2-d15, animals with BM-M2 macrophage infusion and killed at day 15 (n=9). Tubular injury, interstitial fibrosis and pro-inflammatory cytokines were evaluated. A group of n=2 mice were used for in vivo BM-M2 macrophage cell therapy tracking. Results: In vivo tracking demonstrated that macrophages coming from the cell therapy were mainly recruited in liver although some of them finally reached the obstructed kidney. However, UUO mice treated with BM-M2 macrophage cell therapy, showed similar structural renal damage (IFTA and fibronectin scores at days 9 and 15) Conclusions: BM-M2 macrophage cell therapy had no reparative effects in the UUO mice model. Our results suggest that M2 macrophages reaching the obstructed kidney switch their phenotype to M1. (Figure Presented).