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Enhanced homing of mesenchymal stem cells to the ischemic myocardium by ultrasound-targeted microbubble destruction
Authors:Zhong Shigen  Shu Shiyu  Wang Zhigang  Luo Jie  Zhong Weiying  Ran Haitao  Zheng Yuanyi  Yin Yuehui  Ling Zhiyu
Affiliation:a Institute of Ultrasound Imaging, Chongqing Medical University, Chongqing 400010, China
b Department of Anaesthesiology, Children’s Hospital, Chongqing Medical University, Key laboratory of Pediatrics in Chongqing (CSTC2009 CA5002), Chongqing 400014, China
c Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
d Department of Cardiology, the Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China
Abstract:In recent years, ultrasound-targeted microbubble destruction (UTMD) has been utilised for the targeted delivery of stem cells. We tested the effects of the myocardial micro-environment changes induced by UTMD on promoting the homing of mesenchymal stem cells (MSCs) to the ischemic myocardium. Dogs were randomly divided into two groups and treated with or without UTMD after the establishment of myocardial infarction models. 4,6-diamino-2-phenyl indole (DAPI) labelled MSCs were transplanted via coronary injections 2 weeks after myocardial infarction in both groups. The results from real-time PCR and western blot analyses indicated that the expression of various cytokines in UTMD-treated dogs was much higher than that observed in non-treated dogs. Histopathological findings demonstrate that ultrasound at a frequency of 1 MHz and an intensity of 1.0 W/cm2 provoked inflammatory reactions with mild myocardial damage. Myocardial microenvironment changes caused by UTMD may promote the homing of MSCs to the ischemic myocardium. This non-invasive technique may be a promising method for cardiac cell transplantation therapy.
Keywords:Ultrasound   Microbubble   Mesenchymal stem cell   Homing   Microenvironment
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