Investigation of Cellular and Molecular Responses to Pulsed Focused Ultrasound in a Mouse Model

被引:68
作者
Burks, Scott R. [1 ,3 ]
Ziadloo, Ali [1 ]
Hancock, Hilary A. [2 ]
Chaudhry, Aneeka [1 ]
Dean, Dana D. [1 ]
Lewis, Bobbi K. [1 ]
Frenkel, Victor [2 ]
Frank, Joseph A. [1 ,4 ]
机构
[1] NIH, Frank Lab, Ctr Clin, Bethesda, MD 20892 USA
[2] NIH, Mol Imaging Lab, Ctr Clin, Bethesda, MD 20892 USA
[3] Ctr Clin, Imaging Sci Training Program, Bethesda, MD USA
[4] Natl Inst Biomed Imaging & Bioengn, Intramural Res Program, NIH, Bethesda, MD USA
基金
美国国家卫生研究院;
关键词
SKELETAL-MUSCLE INJURY; ENDOTHELIAL-CELLS; IN-VITRO; SOLID TUMORS; BLOOD; HIFU; MECHANOTRANSDUCTION; DELIVERY; CANCER; MRI;
D O I
10.1371/journal.pone.0024730
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Continuous focused ultrasound (cFUS) has been widely used for thermal ablation of tissues, relying on continuous exposures to generate temperatures necessary to induce coagulative necrosis. Pulsed FUS (pFUS) employs non-continuous exposures that lower the rate of energy deposition and allow cooling to occur between pulses, thereby minimizing thermal effects and emphasizing effects created by non-thermal mechanisms of FUS (i.e., acoustic radiation forces and acoustic cavitation). pFUS has shown promise for a variety of applications including drug and nanoparticle delivery; however, little is understood about the effects these exposures have on tissue, especially with regard to cellular pro-homing factors (growth factors, cytokines, and cell adhesion molecules). We examined changes in murine hamstring muscle following pFUS or cFUS and demonstrate that pFUS, unlike cFUS, has little effect on the histological integrity of muscle and does not induce cell death. Infiltration of macrophages was observed 3 and 8 days following pFUS or cFUS exposures. pFUS increased expression of several cytokines (e. g., IL-1 alpha, IL-1 beta, TNF alpha, INF gamma, MIP-1 alpha, MCP-1, and GMCSF) creating a local cytokine gradient on days 0 and 1 post-pFUS that returns to baseline levels by day 3 post-pFUS. pFUS exposures induced upregulation of other signaling molecules (e.g., VEGF, FGF, PlGF, HGF, and SDF-1 alpha) and cell adhesion molecules (e. g., ICAM-1 and VCAM-1) on muscle vasculature. The observed molecular changes in muscle following pFUS may be utilized to target cellular therapies by increasing homing to areas of pathology.
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页数:10
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