Adjunctive mesenchymal stem/stromal cells augment microvascular function in poststenotic kidneys treated with low-energy shockwave therapy.,Journal of Cellular Physiology

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Adjunctive mesenchymal stem/stromal cells augment microvascular function in poststenotic kidneys treated with low-energy shockwave therapy.
Journal of Cellular Physiology ( IF 4.5 ) Pub Date : 2020-05-19 , DOI: 10.1002/jcp.29794
Xiao-Jun Chen _{1,

2} , Xin Zhang ₁ , Kai Jiang ₁ , James D Krier ₁ , Xiangyang Zhu ₁ , Sabena Conley ₁ , Amir Lerman ₃ , Lilach O Lerman _{1,

3}

Affiliation

Effective therapeutic strategies are needed to preserve renal function in patients with atherosclerotic renal artery stenosis (ARAS). Low‐energy shockwave therapy (SW) and adipose tissue‐derived mesenchymal stem/stromal cells (MSCs) both stimulate angiogenesis repair of stenotic kidney injury. This study tested the hypothesis that intrarenal delivery of adipose tissue‐derived MSCs would enhance the capability of SW to preserve stenotic kidney function and structure. Twenty‐two pigs were studied after 16 weeks of ARAS, ARAS treated with a SW regimen (bi‐weekly for 3 weeks) with or without subsequent intrarenal delivery of adipose tissue‐derived MSCs and controls. Four weeks after treatment, single‐kidney renal blood flow (RBF) before and after infusion of acetylcholine, glomerular filtration rate (GFR), and oxygenation were assessed in vivo and the renal microcirculation, fibrosis, and oxidative stress ex vivo. Mean arterial pressure remained higher in ARAS, ARAS + SW, and ARAS + SW + MSC compared with normal. Both SW and SW + MSC similarly elevated the decreased stenotic kidney GFR and RBF observed in ARAS to normal levels. Yet, SW + MSC significantly improved RBF response to acetylcholine in ARAS, and attenuated capillary loss and oxidative stress more than SW alone. Density of larger microvessels was similarly increased by both interventions. Therefore, although significant changes in functional outcomes were not observed in a short period of time, adjunct MSCs enhanced pro‐angiogenic effect of SW to improve renal microvascular outcomes, suggesting this as an effective stratege for long‐term management of renovascular disease.

中文翻译：

辅助间充质干/基质细胞增强了低能量冲击波治疗后狭窄肾脏的微血管功能。

需要有效的治疗策略来保护动脉粥样硬化性肾动脉狭窄 (ARAS) 患者的肾功能。低能量冲击波疗法 (SW) 和脂肪组织来源的间充质干/基质细胞 (MSC) 均能刺激狭窄性肾损伤的血管生成修复。本研究验证了以下假设：脂肪组织来源的 MSC 的肾内递送将增强 SW 保留狭窄肾功能和结构的能力。在 ARAS 治疗 16 周后对 22 头猪进行了研究，ARAS 用 SW 方案（每两周一次，持续 3 周）治疗，有或没有随后肾内递送脂肪组织来源的 MSCs 和对照。治疗后 4 周，乙酰胆碱输注前后单肾肾血流量 (RBF)、肾小球滤过率 (GFR)、体内评估和氧合，体外评估肾脏微循环、纤维化和氧化应激。与正常情况相比，ARAS、ARAS + SW 和 ARAS + SW + MSC 的平均动脉压仍然较高。SW 和 SW + MSC 同样将 ARAS 中观察到的狭窄肾 GFR 和 RBF 降低至正常水平。然而，SW + MSC 显着改善了 ARAS 中对乙酰胆碱的 RBF 反应，并且比单独使用 SW 更能减轻毛细血管损失和氧化应激。两种干预措施同样增加了较大微血管的密度。因此，虽然在短时间内没有观察到功能结果的显着变化，但辅助 MSCs 增强了 SW 的促血管生成作用，以改善肾脏微血管结果，表明这是长期管理肾血管疾病的有效策略。

更新日期：2020-05-19

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