Adipose tissue-derived mesenchymal stem cells improve revascularization outcomes to restore renal function in swine atherosclerotic renal artery stenosis.
Adipose tissue-derived mesenchymal stem cells improve revascularization outcomes to restore renal function in swine atherosclerotic renal artery stenosis.
复制标题
DOI：
10.1002/stem.1047
复制
发表时间：
2012-05
期刊：
影响因子：
5.2
通讯作者：
Lerman, Lilach O.
中科院分区：
文献类型：
--
作者：
Eirin, Alfonso;Zhu, Xiang-Yang;Krier, James D.;Tang, Hui;Jordan, Kyra L.;Grande, Joseph P.;Lerman, Amir;Textor, Stephen C.;Lerman, Lilach O.
需要肾脏保护策略来改善动脉粥样硬化性肾动脉狭窄（ARAS）患者的肾脏结局。脂肪组织来源的间充质干细胞（MSCs）可以促进肾脏再生，但其减轻ARAS细胞损伤和恢复肾脏修复的潜力尚未被探索。我们假设补充MSC作为经皮腔内肾血管成形术（PTRA）的辅助手段，可以恢复ARAS猪肾细胞的完整性并改善肾功能。在ARAS 16周后、PTRA和支架植入术后4周的ARAS（伴或不伴MSC（10×106个细胞）的辅助肾内递送）和对照组研究了4组猪（每组n=7）。使用多探测器计算机断层扫描（CT）测量狭窄肾血流量（肾血流量[RBF]）和肾小球滤过率（GFR）。离体评价肾微血管结构（micro-CT）、纤维化、炎症和氧化应激。PTRA成功后四周，所有血运重建组的平均动脉压下降至相似水平。与正常相比，ARAS（p=0.01和p=0.02）和ARAS+PTRA（p=0.02和p=0.03）中狭窄肾GFR和RBF保持降低，但在ARAS+PTRA+MSC中升高至正常水平（p=0.34和p=0.46 vs.正常）。间质纤维化、炎症、微血管稀疏和氧化应激仅在PTRA+ MSC处理的猪中减弱。MSC的单次肾内递送结合肾血运重建恢复了肾血流动力学和功能，并减少了炎症、凋亡、氧化应激、微血管损失和纤维化。这项研究表明，在慢性实验性肾血管疾病中，MSC与PTRA联合使用时，在恢复肾功能方面具有独特和新颖的治疗潜力。
Reno-protective strategies are needed to improve renal outcomes in patients with atherosclerotic renal artery stenosis (ARAS). Adipose tissue-derived mesenchymal stem cells (MSCs) can promote renal regeneration, but their potential for attenuating cellular injury and restoring kidney repair in ARAS has not been explored. We hypothesized that replenishment of MSC as an adjunct to percutaneous transluminal renal angioplasty (PTRA) would restore renal cellular integrity and improve renal function in ARAS pigs. Four groups of pigs (n=7 each) were studied after 16 weeks of ARAS, ARAS 4 weeks after PTRA and stenting with or without adjunct intra-renal delivery of MSC (10×106 cells), and controls. Stenotic kidney blood flow (renal blood flow[RBF]) and glomerular filtration rate (GFR) were measured using multidetector computer tomography (CT). Renal microvascular architecture (micro-CT), fibrosis, inflammation, and oxidative stress were evaluated ex-vivo. Four weeks after successful PTRA, mean arterial pressure fell to a similar level in all revascularized groups. Stenotic kidney GFR and RBF remained decreased in ARAS (p=0.01 and p=0.02) and ARAS+PTRA (p=0.02 and p=0.03) compared to normal, but rose to normal levels in ARAS+PTRA+MSC (p=0.34 and p=0.46 vs. normal). Interstitial fibrosis, inflammation, microvascular rarefaction, and oxidative stress were attenuated only in PTRA+MSC-treated pigs. A single intra-renal delivery of MSC in conjunction with renal revascularization restored renal hemodynamics and function, and decreased inflammation, apoptosis, oxidative stress, microvascular loss, and fibrosis. This study suggests a unique and novel therapeutic potential for MSC in restoring renal function when combined with PTRA in chronic experimental renovascular disease.
登录
查看更多内容
DOI：
10.1016/j.jss.2010.06.022
发表时间：
2011-06-01
期刊：
The Journal of surgical research
影响因子：
--
作者：
Asanuma H;Vanderbrink BA;Campbell MT;Hile KL;Zhang H;Meldrum DR;Meldrum KK
通讯作者：
Meldrum KK
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：
13.3
作者：
Isles, CG;Robertson, S;Hill, D
通讯作者：
Hill, D
DOI：
10.1073/pnas.0704581104
发表时间：
2007-07-17
影响因子：
11.1
作者：
Hashi, Craig K.;Zhu, Yiqian;Li, Song
通讯作者：
Li, Song
影响因子：
5.2
作者：
Lopez Ponte, Adriana;Marais, Emeline;Domenech, Jorge
通讯作者：
Domenech, Jorge