National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan.
J Transl Med. 2012 Dec 5;10:243. doi: 10.1186/1479-5876-10-243.
Ischemia is the major cause of acute kidney injury (AKI), associated with high mortality and morbidity. Mesenchymal stem cells (MSCs) have multilineage differentiation potential and can be a potent therapeutic option for the cure of AKI.
MSCs were cultured in four groups SNAP (S-nitroso N-acetyl penicillamine), SNAP + Methylene Blue (MB), MB and a control for in vitro analysis. Cultured MSCs were pre-conditioned with either SNAP (100 μM) or MB (1 μM) or both for 6 hours. Renal ischemia was induced in four groups (as in in vitro study) of rats by clamping the left renal padicle for 45 minutes and then different pre-conditioned stem cells were transplanted.
We report that pre-conditioning of MSCs with SNAP enhances their proliferation, survival and engraftment in ischemic kidney. Rat MSCs pre-conditioned with SNAP decreased cell apoptosis and increased proliferation and cytoprotective genes' expression in vitro. Our in vivo data showed enhanced survival and engraftment, proliferation, reduction in fibrosis, significant improvement in renal function and higher expression of pro-survival and pro-angiogenic factors in ischemic renal tissue in SNAP pre-conditioned group of animals. Cytoprotective effects of SNAP pre-conditioning were abrogated by MB, an inhibitor of nitric oxide synthase (NOS) and guanylate cyclase.
The results of these studies demonstrate that SNAP pre-conditioning might be useful to enhance therapeutic potential of MSCs in attenuating renal ischemia reperfusion injury.
缺血是急性肾损伤（AKI）的主要原因，与高死亡率和发病率相关。间充质干细胞（MSCs）具有多能分化潜能，是治疗 AKI 的有效治疗方法。
将 MSCs 在 SNAP（S-亚硝基-N-乙酰青霉胺）、SNAP+亚甲蓝（MB）、MB 和对照 4 组中进行培养，用于体外分析。将培养的 MSCs 用 SNAP（100 μM）或 MB（1 μM）或两者预处理 6 小时。通过夹闭左肾蒂 45 分钟，在 4 组大鼠（如体外研究）中诱导肾缺血，然后移植不同预处理的干细胞。
我们报告说，用 SNAP 预处理 MSC 可增强其在缺血肾脏中的增殖、存活和定植。体外 SNAP 预处理的大鼠 MSCs 减少了细胞凋亡，增加了增殖和细胞保护基因的表达。我们的体内数据显示，SNAP 预处理组动物的存活率和定植率增加，增殖减少，纤维化减少，肾功能显著改善，缺血肾组织中促生存和促血管生成因子的表达增加。NOS（一氧化氮合酶）和鸟苷酸环化酶抑制剂 MB 可消除 SNAP 预处理的细胞保护作用。
这些研究的结果表明，SNAP 预处理可能有助于增强 MSCs 在减轻肾缺血再灌注损伤中的治疗潜力。
