Micro-vesicles derived from bone marrow stem cells protect the kidney both in vivo and in vitro by microRNA-dependent repairing.

Abstract

Micro-vesicles (MVs) from bone mesenchymal stem cells (MSCs) have been shown to contribute to the recovery of damaged kidney. The aims of the present study are to investigate the biological effects and repair mechanisms of MVs. Micro-vesicles were obtained from MSC supernatants. In vitro, the proximal tubular epithelial cells (HK-2) were treated with transforming growth factor (TGF-β1). The expressions of E-cadherin and α-smooth muscle actin (α-SMA) were evaluated. In vitro, the mice were divided into: control, unilateral ureteral obstruction (UUO), UUO+MSC, and UUO+MV group. MVs and MSCs were injected after surgery. The mice were killed 7/14 days after surgery and handled for further tests. The micro-RNA expressions were labeled using the miRCURY Hy3/Hy5 Power labeling kit and hybridized on the miRCURY LNA Array. In vitro, MV reversed transforming growth factor-β1 (TGF-β1)-induced morphological changes, and firmed the expression of E-cadherin and reduced the secretion of α-SMA in HK2 cells. In vivo, the level of blood urea nitrogen (BUN) in the MV and MSC group was lower than the UUO (P < 0.01). The Scr level decreased after 7 days of MV treatment (P < 0.05). Administration of MSC and MV reduced Scr level at day 14 (P < 0.05). The level of serum UA decreased with MV administration (day 7,14, P < 0.01). Herein, a total of 503 expressed miRNAs were detected, of which, 266 were in MSC, including 237 in MVs. Micro-vesicles (MVs) protect kidneys both in vivo and vitro, and MVs are superior to MSCs in some respects. MVs can be a potential therapy in treatment of kidney diseases.