Gong Wang1, Qian Zhang2, Zhongxiong Zhuo1, Shengzheng Wu1, Zheng Liu1, Hongmei Xia1, Kaibin Tan1, Linru Zou1, Ling Gan1, Yunhua Gao3. 1. Department of Ultrasound, Xinqiao Hospital, The Third Military Medical University, Chongqing, 400037, China. 2. Department of Nephrology, Xinqiao Hospital, The Third Military Medical University, Chongqing, China. 3. Department of Ultrasound, Xinqiao Hospital, The Third Military Medical University, Chongqing, 400037, China. xqgaoyh@outlook.com.
Abstract
OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. KEY POINTS: • 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.
OBJECTIVES: 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. METHODS: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. RESULTS: 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. CONCLUSIONS: 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. KEY POINTS: • 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.
Entities:
Keywords:
Bone marrow stromal cells; Homing; Kidney; Microbubble; Ultrasound
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