Arterially Delivered Mesenchymal Stem Cells Prevent Obstruction-Induced Renal Fibrosis

摘要: Background Mesenchymal stem cells (MSCs) hold promise for the treatment of renal disease. While MSCs have been shown to accelerate recovery and prevent acute failure in multiple disease models, effect MSC therapy on chronic obstruction-induced fibrosis has not previously evaluated. Materials Methods Male Sprague-Dawley rats underwent artery injection vehicle or fluorescent-labeled human bone marrow-derived immediately prior sham operation induction left ureteral obstruction (UUO). One 4 wk later, the kidneys were harvested cortex analyzed evidence cell infiltration, epithelial-mesenchymal transition (EMT) as evidenced by E-cadherin/α-smooth muscle actin (α-SMA) expression fibroblast specific protein (FSP+) staining, (collagen content, Masson's trichrome staining), cytokine growth factor activity (ELISA real time RT-PCR). Results Fluorescent-labeled detected in the interstitium kidney up post-obstruction. Arterially delivered significantly reduced α-SMA expression, FSP+ accumulation, total collagen tubulointerstitial fibrosis, while simultaneously preserving E-cadherin suggesting that EMT fibrosis. Exogenous tumor necrosis factor-α (TNF-α) levels, but did alter transforming factor-β1 (TGF-β1), vascular endothelial (VEGF), interleukin-10 (IL-10), (FGF), hepatocyte (HGF) expression. Conclusions Human remain viable several weeks after delivery into provide protection against mechanism MSCs-induced during remains unclear, our results demonstrate alterations TNF-α production may be involved.