Mesenchymal stem cells improve medullary inflammation and fibrosis after revascularization of swine atherosclerotic renal artery stenosis.
Mesenchymal stem cells improve medullary inflammation and fibrosis after revascularization of swine atherosclerotic renal artery stenosis.
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DOI：
10.1371/journal.pone.0067474
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Lerman LO
中科院分区：
文献类型：
--
作者：
Ebrahimi B;Eirin A;Li Z;Zhu XY;Zhang X;Lerman A;Textor SC;Lerman LO
动脉粥样硬化性肾动脉狭窄（ARAS）会升高血压并降低肾功能。单纯狭窄肾动脉血运重建不能恢复肾髓质结构和功能。本研究验证了在经皮肾血管成形术（PTRA）中加入间充质干细胞（MSC）可以恢复支架-肾小管转运功能并减轻其重塑的假设。将27头猪分为高胆固醇饮食和肾动脉狭窄组和正常对照组。ARAS诱导后6周，两组分别接受PTRA单独治疗或PTRA补充脂肪组织来源的MSC（10×106个细胞，肾内）。4周后进行多探测器计算机断层扫描和血氧水平依赖性（BOLD）MRI研究，以评估肾脏血流动力学和功能，并在几天后收集组织进行组织学和显微CT成像。PTRA有效地降低血压，但髓质血管密度仍然很低。MSC的加入改善了ARAS+PTRA+MSC中的骨髓血管形成，并增加了血管生成信号，包括血管内皮生长因子及其受体（FLK-1）和缺氧诱导因子-1 α的蛋白表达。ARAS+PTRA+MSC也显示炎症减轻，尽管氧化应激仍然升高。BOLD-MRI显示，MSC使氧依赖性肾小管对呋塞米的反应正常化（正常、ARAS、ARAS+PTRA和ARAS+PTRA+MSC分别为-4.3 0. 9、-0.1 ±0.4、-1.6 ±0.9和-3.6 ±1.0 s-1，p<0.05），这与肾小管损伤评分降低相关（R2 = 0.33，p = 0.02）。 因此，除了PTRA之外，连续性MSC递送减少炎症、纤维形成和血管重塑，并恢复肾脏髓质中的氧依赖性肾小管功能，尽管可能需要额外的干预来减少氧化应激。这项研究支持发展以细胞为基础的策略，在ARAS的肾保护。
Atherosclerotic renal artery stenosis (ARAS) raises blood pressure and can reduce kidney function. Revascularization of the stenotic renal artery alone does not restore renal medullary structure and function. This study tested the hypothesis that addition of mesenchymal stem cells (MSC) to percutaneous transluminal renal angioplasty (PTRA) can restore stenotic-kidney medullary tubular transport function and attenuate its remodeling. Twenty-seven swine were divided into three ARAS (high-cholesterol diet and renal artery stenosis) and a normal control group. Six weeks after ARAS induction, two groups were treated with PTRA alone or PTRA supplemented with adipose-tissue-derived MSC (10×106 cells intra-renal). Multi-detector computed tomography and blood-oxygenation-level-dependent (BOLD) MRI studies were performed 4 weeks later to assess kidney hemodynamics and function, and tissue collected a few days later for histology and micro-CT imaging. PTRA effectively decreased blood pressure, yet medullary vascular density remained low. Addition of MSC improved medullary vascularization in ARAS+PTRA+MSC and increased angiogenic signaling, including protein expression of vascular endothelial growth-factor, its receptor (FLK-1), and hypoxia-inducible factor-1α. ARAS+PTRA+MSC also showed attenuated inflammation, although oxidative-stress remained elevated. BOLD-MRI indicated that MSC normalized oxygen-dependent tubular response to furosemide (-4.3±0.9, −0.1±0.4, −1.6±0.9 and −3.6±1.0 s−1 in Normal, ARAS, ARAS+PTRA and ARAS+PTRA+MSC, respectively, p<0.05), which correlated with a decrease in medullary tubular injury score (R2 = 0.33, p = 0.02). Therefore, adjunctive MSC delivery in addition to PTRA reduces inflammation, fibrogenesis and vascular remodeling, and restores oxygen-dependent tubular function in the stenotic-kidney medulla, although additional interventions might be required to reduce oxidative-stress. This study supports development of cell-based strategies for renal protection in ARAS.
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影响因子：
9.1
作者：
Lerman, Lilach O.;Textor, Stephen C.;Grande, Joseph P.
通讯作者：
Grande, Joseph P.
影响因子：
6.1
作者：
Gatti, Stefano;Bruno, Stefania;Camussi, Giovanni
通讯作者：
Camussi, Giovanni
DOI：
10.1152/ajprenal.00159.2010
发表时间：
2010-07-01
影响因子：
4.2
作者：
Urbieta-Caceres, Victor H.;Lavi, Ronit;Lerman, Lilach O.
通讯作者：
Lerman, Lilach O.
影响因子：
6.1
作者：
Biancone, Luigi;Bruno, Stefania;Camussi, Giovanni
通讯作者：
Camussi, Giovanni
影响因子：
19.7
作者：
Daghini, Elena;Primak, Andrew N.;Lerman, Lilach O.
通讯作者：
Lerman, Lilach O.