MICROVESCICOLE (MV) DERIVATE DA CELLULE PROGENITRICI ENDOTELIALI (EPC) RIDUCONO LA PROTEINURIA E ACCELLERANO LA REMISSIONE ISTOLOGICA NELLA GLOMERULONEFRITE (GN) ANTI-THY 1.1

[Machine translation] Introduction. The loss of glomerular capillaries is associated with glomerulosclerosis and progression to chronic renal failure. The use of stem cells to improve angiogenesis is proposed to reduce kidney damage. EPC are circulating stem cells capable of releasing MVs, biologically active particles that stimulate angiogenesis through RNA transfer., purpose. Evaluate whether MVs released by EPC accelerate glomerular repair in anti-Thy1.1 GN. , Materials and Methods. MVs separated from EPC supernatant by ultracentrifugation and characterized by protein and RNA content. Treated rats: 1) saline; 2) 400 mcg AntiThy 1.1; 3) AntiThy 1.1+250 mcg/mL MV, 4) AntiThy 1.1+250 mcg/mL MV pre-treated with 1 U/ml RNase. MV control of human fibroblasts. Effects of MV on isolated human glomerular, podocyte and mesangial endothelial cells have been studied. Also use MVs treated with 1 U/ml RNase or produced by EPC with siRNA Dicer, an essential enzyme for microRNA production., Results. MVs cause decreased proteinuria and improved renal function, reduced mesangiolysis, microaneurysms, apoptosis and leukocyte infiltration. MVs preserve glomerular integrity (maintained expression of RECA and synaptopodin). Marked MVs are incorporated into the endothelium and podocytes and promote glomerular endothelial angiogenesis, podocyte functionality and reduce complement-mediated damage in the mesangium. The protective effect of MV is reduced if pretreated with RNase or Dicer siRNA., Conclusions. MVs accelerate repair in anti-Thy1.1 GN while maintaining glomerular integrity. Protective effect attributable to MV internalization in endothelium, podocytes and mesangium for the transfer of mRNA and microRNA to damaged glomerular cells