Arterially delivered mesenchymal stem cells prevent obstruction-induced renal fibrosis.
Arterially delivered mesenchymal stem cells prevent obstruction-induced renal fibrosis.
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DOI：
10.1016/j.jss.2010.06.022
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发表时间：
2011-06-01
期刊：
影响因子：
--
通讯作者：
Meldrum KK
中科院分区：
文献类型：
--
作者：
Asanuma H;Vanderbrink BA;Campbell MT;Hile KL;Zhang H;Meldrum DR;Meldrum KK
间充质干细胞（MSC）有望治疗肾脏疾病。虽然 MSC 已被证明可以在多种疾病模型中加速恢复并预防急性肾衰竭，但 MSC 治疗对慢性阻塞性肾纤维化的效果此前尚未得到评估。雄性 Sprague-Dawley 大鼠在假手术或诱导左侧输尿管梗阻 (UUO) 之前立即接受肾动脉注射载体或荧光标记的人骨髓来源的 MSC。 1 或 4 周后，收获肾脏并分析肾皮质的干细胞浸润证据、上皮-间质转化 (EMT)（通过 E-钙粘蛋白/α-平滑肌肌动蛋白 (α-SMA) 表达和成纤维细胞特异性蛋白 (FSP+) 染色证明）、肾纤维化（胶原含量、Masson 三色染色）和 细胞因子和生长因子活性（ELISA 和实时 RT-PCR）。梗阻后 4 周内，在肾间质中检测到荧光标记的 MSC。动脉输送的 MSC 显着降低梗阻诱导的 α-SMA 表达、FSP+ 细胞积累、总胶原含量和肾小管间质纤维化，同时保留 E-钙粘蛋白表达，表明 MSC 可以预防梗阻诱导的 EMT 和肾纤维化。外源性MSC降低了阻塞诱导的肿瘤坏死因子-α（TNF-α）水平，但没有改变转化生长因子-β1（TGF-β1）、血管内皮生长因子（VEGF）、白细胞介素-10（IL-10）、成纤维细胞生长因子（FGF）或肝细胞生长因子（HGF）的表达。人骨髓来源的间充质干细胞在输送到肾脏后几周仍保持活力，并提供针对梗阻诱导的 EMT 和慢性肾纤维化的保护作用。虽然梗阻期间 MSC 诱导的肾脏保护机制尚不清楚，但我们的结果表明可能涉及 TNF-α 产生的改变。
Mesenchymal stem cells (MSCs) hold promise for the treatment of renal disease. While MSCs have been shown to accelerate recovery and prevent acute renal failure in multiple disease models, the effect of MSC therapy on chronic obstruction-induced renal fibrosis has not previously been evaluated. Male Sprague-Dawley rats underwent renal artery injection of vehicle or fluorescent-labeled human bone marrow-derived MSCs immediately prior to sham operation or induction of left ureteral obstruction (UUO). One or 4 weeks later, the kidneys were harvested and the renal cortex analyzed for evidence of stem cell infiltration, epithelial-mesenchymal transition (EMT) as evidenced by E-cadherin/α-smooth muscle actin (α-SMA) expression and fibroblast specific protein (FSP+) staining, renal fibrosis (collagen content, Masson’s trichrome staining), and cytokine and growth factor activity (ELISA and real time RT-PCR). Fluorescent-labeled MSCs were detected in the interstitium of the kidney up to 4 weeks post-obstruction. Arterially delivered MSCs significantly reduced obstruction-induced α-SMA expression, FSP+ cell accumulation, total collagen content, and tubulointerstitial fibrosis, while simultaneously preserving E-cadherin expression, suggesting that MSCs prevent obstruction-induced EMT and renal fibrosis. Exogenous MSCs reduced obstruction-induced tumor necrosis factor-α (TNF-α) levels, but did not alter transforming growth factor-β1 (TGF-β1), vascular endothelial growth factor (VEGF), interleukin-10 (IL-10), fibroblast growth factor (FGF), or hepatocyte growth factor (HGF) expression. Human bone marrow-derived MSCs remain viable several weeks after delivery into the kidney and provide protection against obstruction-induced EMT and chronic renal fibrosis. While the mechanism of MSCs-induced renal protection during obstruction remains unclear, our results demonstrate that alterations in TNF-α production may be involved.
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影响因子：
4.5
作者：
Wong, Chee-Yin;Cheong, Soon-Keng;Leong, Chooi-Fun
通讯作者：
Leong, Chooi-Fun
影响因子：
37.8
作者：
Rehman, J;Traktuev, D;March, KL
通讯作者：
March, KL
影响因子：
4
作者：
Kano, MR;Morishita, Y;Miyazawa, K
通讯作者：
Miyazawa, K
影响因子：
2.6
作者：
Devine, SM;Bartholomew, AM;Hoffman, R
通讯作者：
Hoffman, R
DOI：
10.1016/s0167-4889(98)00143-8
发表时间：
1998-12-10
影响因子：
5.1
作者：
Barraclough, R
通讯作者：
Barraclough, R