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논문분류	춘계학술대회 초록집
제목	Tonsil-derived Mesenchymal Stem Cells ameliorated Renal Tubular Damage in Gentamicin-induced Acute Kidney Injury (AKI) via Modulation of Oxidative Stress and Apoptosis
저자	Eun-Sun Ryu*, Jiyeon Ko, Dal-Ah Kim, Sung Min Jung, Dong-Ryeol Ryu, Seung-Jung Kim, Kyu-Bok Choi, Duk-Hee Kang
출판정보	2016; 2016(1):
키워드	Tonsil-derived Mesenchymal Stem Cell, AKI, Oxidative stress, Apoptosis
초록	Background: Gentamicin (GM)-induced AKI occurs in 10-20% of treated patients.GM is accumulated in renal epithelial cells, which causes the loss of the brush border, apoptosis and overt necrosis of renal tubules. Stem cell therapy has recently emerged as a potential therapeutic tool for several diseases including AKI, however the mechanisms underlying the improvement in kidney function provided by stem cell therapy remain unclear. Tonsil-derived mesenchymal stem cells (T-MSCs) which are isolated from tonsils of the patient undergoing tonsillectomy are proposed as a new source of stem cell, potentially applicable for cell-based therapy. The aim of this study is to investigate the therapeutic potential of T-MSCs in the treatment of AKI induced by GM. Methods: Twenty male Sprague-Dawley rats were divided into four groups: Control, GM (140 mg/kg/day, ip for 10 days), GM+T-MSCs (1x107cells, intravenous injection at1st day after the 1st GM injection) and T-MSC group. To determine the intra-renal localization of T-MSCs, T-MSCs were labeled with PKH-26 red fluorescence before infusion. Measurement of BUN, Cr, proteinuria and histologic analysis including TUNEL staining were performed on 16 days of GM injection. Oxidative stress in the kidney was assessed by measuring urinary hydroxy-dG (OH-dG) and the expression of glutathione peroxidase (GPX), catalase and superoxide dismutase (SOD). Effect of T-MSC on renal tubular cells was also evaluated using a transwell co-culture system of NRK cells and T-MSC. Intracellular ROS was analyzed by measuring NOX activity, H2O2 generation, and NOX mRNA expressions. Results: The infusion of T-MSCs preserved renal function with a decrease in BUN and proteinuria. T-MSCs also ameliorated renal tubular dilatation and apoptosis of renal tubular cells in the rats with GM-induced AKI. The infusion of T-MSCs down-regulated the expression of Bax, Cytochrome c, Cleaved caspase-9 and -3 with an up-regulation of Bcl-2 in renal cortex. PKH-26-labeled T-MSCs were observed in damaged tubules in GM+T-MSCs group. T-MSC also decreased urinary hydroxy-dG level, a marker of oxidative stress, and increased anti-oxidants including GPX and SOD2 in renal cortex. In-vitro study revealed that co-culture of T-MSC with NRK cells ameliorated GM-induced apoptosis and increase in H2O2 generation and NOX mRNA expressions. Conclusion: Our results suggest that T-MSCs protect the kidney from GM-induced AKI, possibly via the mechanism of modulation of oxidative stress and apoptosis of renal tubular cells.
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