title: Targeted delivery of bone mesenchymal stem cells by ultrasound destruction of microbubbles promotes kidney recovery in acute kidney injury.
abstract: The aim of the present study was to explore whether ultrasound microbubble destruction augments site-targeted engraftment of bone marrow mesenchymal stem cells (BM-MSCs) to kidney tissue and promotes recovery of the kidney in acute kidney injury (AKI) in rats. AKI was induced by the subcutaneous injection of mercuric chloride (HgCl₂). Forty Sprague-Dawley (SD) rats were randomly divided into the following groups after the establishment of rat models of AKI (n = 10): (1) Model group alone (control group); (2) 1.0 W/cm² ultrasound (US) + microbubble (MB) (US/MB group); (3) MSCs group; and (4) 1.0 W/cm² US+MB + MSCs group (US/MB + MSCs group). The number of 4',6-diamidino-2-phenylindole (DAPI) labelled MSCs was evaluated by fluorescence microscopy and real-time polymerase chain reaction (RT-PCR) and Western blotting and histological examination were performed 7 days after MSCs transplantation. It was observed via fluorescence microscopy that the number of DAPI-labelled MSCs in the kidney for the US/MB + MSCs group was significantly more than the MSCs group (p < 0.05). The results from RT-PCR revealed that the US/MB and US/MB + MSCs groups markedly increased the level of inter-cellular adhesion molecule 1 (ICAM-1) messenger ribonucleic acid (mRNA) compared with the control group and the MSCs group (p < 0.05). Western blot analysis showed that the expression of hepatocyte growth factor (HGF) and epidermal growth factor (EGF) in the US/MB + MSCs group were markedly increased compared with the all other groups (p < 0.01). The extent of tubular necrosis and dilation was significantly milder in the US/MB + MSCs group (acoustic exposure conditions: 5s at 1 MHz and 1.0 W/cm² with a 5s pause, totalling 60 s) than the all other groups (p < 0.05). Microbubble destruction by 1.0 W/cm² ultrasound can promote both the homing of BM-MSCs to kidney tissue and the recovery of the kidney in AKI in rats.
authors.affiliation: Department of Ultrasound, Sir Run Run Shaw Hospital, Zhejiang University Medical College, Hangzhou, China.
authors.forename: Hai-Lin
authors.initials: HL
authors.lastname: Tang
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: Wang
authors.forename: Qiao
authors.initials: Q
authors.lastname: Li
authors.forename: Hai-Tao
authors.initials: HT
authors.lastname: Ran
authors.forename: Yuan-Yi
authors.initials: YY
authors.lastname: Zheng
authors.forename: Jian-Li
authors.initials: JL
authors.lastname: Ren
authors.forename: Zhi-Yu
authors.initials: ZY
authors.lastname: Ling
authors.forename: Ao
authors.initials: A
authors.lastname: Li
authors.forename: Bowen
authors.initials: B
authors.lastname: Zhao
mesh_terms: D058186:Acute Kidney Injury / Q000000981:diagnostic imaging / Q000378:metabolism / Q000628:therapy*; D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D007211:Indoles; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D045423:Microbubbles; D008856:Microscopy, Fluorescence; D010641:Phenotype; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D014465:Ultrasonics; D014463:Ultrasonography
chemical_list: D007211:Indoles; D018799:Intercellular Adhesion Molecule-1; C007293:DAPI