Bone marrow stem cells-derived microvesicles protect against renal injury in the mouse remnant kidney model

Aims: Several studies have demonstrated administration of mesenchymal stem cells (MSC) could reverse kidney injury by paracrine mechanisms rather than by MSC transdifferentiation. Recently, a few researchers found microvesicles (MV) derived from MSC might be a paracrine mechanism for cell-to-cell communication. The aim of this study was to investigate the repair effects of MV in a 5/6 subtotal nephrectomy (Nx) mice model. Methods: The animals were randomly divided into four groups: Control, Nx, Nx + MSC and Nx + MV group. MSC were injected (1 x 106/mouse) through caudal vein in Nx + MSC group at the second day after the surgery and MV were injected (30 mu g/mouse) through caudal vein in Nx + MV group on alternate days. Mice were killed on day 7 after the first time of administration. Blood urea nitrogen (BUN), serum creatinine (Scr), uric acid (UA) and proteinuria were evaluated. Histopathology of kidney was analysed. Results: In Nx mice, the levels of Scr, UA and proteinuria were significantly decreased with administration of MV and MSC (P < 0.05). The remnant kidneys of MV and MSC-treated Nx mice showed less fibrosis, interstitial lymphocyte infiltrates and less or absent tubular atrophy compared with the untreated Nx group. The Histological Score of Kidney in untreated mice was 3.13 +/- 0.74, while in the MSC-treated group it was 1.67 +/- 0.47 and in the MV-treated group it was 1.80 +/- 0.44, nearly preserving normal morphology of the kidney (P < 0.01). Conclusion: This study showed MV protects against renal injury induced by 5/6 Nx, which could mimic the role of MSC in kidney repair. The research showed a newly potential therapeutic approach to kidney diseases.