Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota 55905, USA.
Stem Cells. 2012 May;30(5):1030-41. doi: 10.1002/stem.1047.
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 intrarenal delivery of MSC (10 × 10(6) 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 = .01 and p = .02) and ARAS + PTRA (p = .02 and p = .03) compared with normal but rose to normal levels in ARAS + PTRA + MSC (p = .34 and p = .46 vs. normal). Interstitial fibrosis, inflammation, microvascular rarefaction, and oxidative stress were attenuated only in PTRA + MSC-treated pigs. A single intrarenal 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.
需要肾保护策略来改善粥样硬化性肾动脉狭窄（ARAS）患者的肾脏预后。脂肪组织来源的间充质干细胞（MSCs）可促进肾脏再生，但它们在减轻细胞损伤和恢复 ARAS 中肾脏修复的潜力尚未得到探索。我们假设，将 MSC 补充作为经皮腔内肾血管成形术（PTRA）的辅助手段，将恢复 ARAS 猪的肾细胞完整性并改善肾功能。在 ARAS 16 周后，4 组猪（每组 7 只）接受了研究：ARAS、PTRA 和支架置入后 4 周，以及 ARAS 并有或没有辅助性肾内 MSC（10×10^6 细胞）输注，和对照组。使用多排计算机断层扫描（CT）测量狭窄肾脏血流（肾血流[RBF]）和肾小球滤过率（GFR）。通过离体评估肾微血管结构（微 CT）、纤维化、炎症和氧化应激。在成功的 PTRA 后 4 周，所有再血管化组的平均动脉压均降至相似水平。与正常相比，ARAS（p =.01 和 p =.02）和 ARAS + PTRA（p =.02 和 p =.03）的狭窄肾脏 GFR 和 RBF 仍然降低，但在 ARAS + PTRA + MSC 中升高至正常水平（p =.34 和 p =.46 与正常相比）。仅在 PTRA + MSC 治疗的猪中，间质纤维化、炎症、微血管稀疏和氧化应激减轻。单次肾内 MSC 输注联合肾血管重建可恢复肾功能和血流动力学，并降低炎症、细胞凋亡、氧化应激、微血管丢失和纤维化。这项研究表明，在慢性实验性肾血管疾病中，MSC 与 PTRA 联合使用具有恢复肾功能的独特和新颖的治疗潜力。
