title: Ultrasound targeted microbubble destruction promotes angiogenesis and heart function by inducing myocardial microenvironment change.
abstract: The myocardial microenvironment plays a decisive role in the survival, migration and differentiation of stem cells. We studied myocardial micro-environmental changes induced by ultrasound-targeted microbubble destruction (UTMD) and their influence on the transplantation of mesenchymal stem cells (MSCs). Various intensities of ultrasound were applied to the anterior chest in canines with myocardial infarction after intravenous injection of microbubbles. The expression of cytokines and adhesion molecules in the infarcted area of the myocardium was detected after three sessions of UTMD in 1 wk. Real-time quantitative reverse transcription polymerase chain reaction (RTQ-PCR) showed that the expression of vascular cell adhesion molecule-1 (VCAM-1), stromal cell-derived factor-1 (SDF-1) and vascular endothelial growth factor (VEGF) in the 1.5 W/cm(2) and 1 W/cm(2) groups was markedly increased compared with the 0.5 W/cm(2) or the control groups (3.8- to 4.7-fold, p < 0.01), and the expression of interleukin-1β (IL-1β) in the 1.5 W/cm(2) group was increased twofold over the 1.0 W/cm(2) group, whereas the 0.5 W/cm(2) group experienced no significant changes. UTMD at 1.0 W/cm(2) was performed as previously described before mesenchymal stem cell (MSC) transplantation. Myocardial perfusion, angiogenesis and heart function were investigated before and 1 month after MSC transplantation. Coronary angiography and 99mTc-tetrofosmin scintigraphy revealed that myocardial perfusion was markedly improved after UTMD + MSCs treatment (p < 0.05). At echocardiographic analysis, heart function and the wall motion score index were significantly improved by UTMD + MSCs treatment compared with MSCs or UTMD alone and the control. In a canine model of myocardial infarction, therapeutic effects were markedly enhanced by MSC transplantation after the myocardial micro-environmental changes induced by UTMD; therefore, this novel method may be useful as an efficient approach for cellular therapy.
authors: Department of Cardiology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
authors: Zhi-Yu
authors: ZY
authors: Ling
authors: Shi-yu
authors: SY
authors: Shu
authors: Shi-Gen
authors: SG
authors: Zhong
authors: Jie
authors: J
authors: Luo
authors: Li
authors: L
authors: Su
authors: Zeng-Zhang
authors: ZZ
authors: Liu
authors: Xian-Bin
authors: XB
authors: Lan
authors: Geng-Biao
authors: GB
authors: Yuan
authors: Yuan-Yi
authors: YY
authors: Zheng
authors: Hai-Tao
authors: HT
authors: Ran
authors: Zhi-Gang
authors: ZG
authors: Wang
authors: Yue-Hui
authors: YH
authors: Yin
mesh_terms: D000818:Animals; D003131:Combined Modality Therapy; D004285:Dogs; D005466:Fluorocarbons / Q000528:radiation effects / Q000627:therapeutic use*; D045423:Microbubbles / Q000627:therapeutic use; D009203:Myocardial Infarction / Q000503:physiopathology* / Q000628:therapy*; D018919:Neovascularization, Physiologic / Q000528:radiation effects*; D011829:Radiation Dosage; D013010:Sonication / Q000379:methods*; D055153:Stem Cell Niche / Q000528:radiation effects*; D033581:Stem Cell Transplantation; D016896:Treatment Outcome
chemical_list: D005466:Fluorocarbons; C042852:perflutren
keywords: Angiogenesis; Bone marrow mesenchymal stem cell; Microbubbles; Myocardial infarction; Myocardial microenvironment; Therapeutic ultrasound; Ultrasound-targeted microbubble destruction