Wang Gong, Zhang Qian, Zhuo Zhongxiong, Wu Shengzheng, Liu Zheng, Xia Hongmei, Tan Kaibin, Zou Linru, Gan Ling, Gao Yunhua
Department of Ultrasound, Xinqiao Hospital, The Third Military Medical University, Chongqing, 400037, China.
Department of Nephrology, Xinqiao Hospital, The Third Military Medical University, Chongqing, China.
Eur Radiol. 2016 Sep;26(9):3006-16. doi: 10.1007/s00330-015-4123-3. Epub 2015 Dec 4.
Bone marrow stromal cells (BMSC) transplantation proves successful in treating kidney disease and injury in many studies. However, their reparative capacity is limited by the poor homing ability in vivo, which is decided mainly by the local expression of chemoattractants. Our study explored the mechanical effects of ultrasound targeted microbubble destruction (UTMD) on BMSCs homing ability in treated kidney tissues.
Rats were injected with red fluorescent protein (RFP)-labelled BMSCs and sonicated with microbubble-mediated ultrasound. Then, we tested kidney micro-environment changes induced and their influence on stem cell homing ability.
The results showed that the mechanical effects of UTMD would increase local and transient levels of chemoattractants (i.e. cytokines, integrins and growth factors) in targeted kidney tissues. Transmission electron microscopy showed that vascular endothelial cell was discontinuous in the UTMD group post-treatment, becoming smooth 72 h later. Confocal laser scanning microscopy and RT-PCR showed up to eight times more stem cells in the peritubular regions of experimental kidneys on days 1 and 3 post-treatment compared with the contralateral kidney.
These results confirmed that renal micro-environment changes caused by appropriate UTMD may promote BMSC homing ability toward treated kidney tissues without renal toxicity and cell damage.
• This experiment showed a feasible strategy in promoting stem cell homing ability. • The treatment uses diagnostic ultrasound during enhancement with IV microbubbles. • A suitable micro-environment was important for targeted stem cell homing and retention. • The method is effective for stem cell homing to kidney diseases. • More work is required with larger animals before potential human trials.
多项研究证明，骨髓基质细胞（BMSC）移植在治疗肾脏疾病和损伤方面是成功的。然而，其修复能力受到体内归巢能力差的限制，而归巢能力主要由趋化因子的局部表达决定。我们的研究探讨了超声靶向微泡破坏（UTMD）对经治疗的肾脏组织中BMSC归巢能力的机械效应。
给大鼠注射红色荧光蛋白（RFP）标记的BMSC，并用微泡介导的超声进行超声处理。然后，我们测试了诱导的肾脏微环境变化及其对干细胞归巢能力的影响。
结果表明，UTMD的机械效应会增加靶向肾脏组织中趋化因子（即细胞因子、整合素和生长因子）的局部和瞬时水平。透射电子显微镜显示，UTMD组治疗后血管内皮细胞不连续，72小时后变得光滑。共聚焦激光扫描显微镜和RT-PCR显示，与对侧肾脏相比，治疗后第1天和第3天实验肾脏肾小管周围区域的干细胞数量增加了多达8倍。
这些结果证实，适当的UTMD引起的肾脏微环境变化可能促进BMSC向经治疗的肾脏组织的归巢能力，而不会产生肾毒性和细胞损伤。
• 本实验展示了一种促进干细胞归巢能力的可行策略。• 该治疗在静脉注射微泡增强期间使用诊断超声。• 合适的微环境对于靶向干细胞归巢和滞留很重要。• 该方法对干细胞归巢到肾脏疾病有效。• 在进行潜在的人体试验之前，需要对更大的动物进行更多研究。
