Vascular endoluminal cellular paving using acoustic radiation force

利用声辐射力进行血管腔内细胞铺路

• 批准号: 8403791
• 负责人: Catalin Toma
• 金额: $ 21.63万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-01-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8403791
• 关键词: Acoustics; Acute; Address; Allogenic; Angioplasty; Anticoagulants; Aorta; Area; Arterial Fatty Streak; Arterial Injury; Arteries; Autologous; Automobile Driving; Blood Vessels; Cardiovascular system; Catheters; Cell Communication; Cell Survival; Cells; Chronic; Clinical; Coagulation Process; Collaborations; Complex; Contrast Media; Coronary; Coronary Arteriosclerosis; Coronary artery; Data; Drug Targeting; Effectiveness; Electrostatics; Endothelium; Energy-Generating Resources; Event; FDA approved; Frequencies; Gases; Glycocalyx; Goals; Grant; Healed; Hyperplasia; In Vitro; Injury; Intervention; Lead; Link; Lipids; Mediating; Medicine; Mesenchymal Stem Cells; Methods; Microbubbles; Microbubbles Ultrasound Contrast Medium; Modeling; Morbidity - disease rate; Motion; Natural regeneration; Oryctolagus cuniculus; Outcome; Particle Size; Patients; Pharmaceutical Preparations; Physics; Physiological; Play; Procedures; Radiation; Research; Role; Safety; Stem cells; Stents; Surface; System; Technology; Testing; Therapeutic; Thrombosis; Time; Tissues; Translating; Treatment Efficacy; Ultrasonography; Universities; absorption; base; clinical application; clinically relevant; design; efficacy testing; falls; healing; improved; in vivo; injured; interest; molecular imaging; mortality; multidisciplinary; novel; particle; percutaneous coronary intervention; prevent; radiation effect; repaired; research study; restenosis; restoration; scaffold; sound; tool

ABSTRACT Coronary stents represent an important tool in the armamentarium available to treat symptomatic atherosclerotic plaques, with over 1 million procedures performed annually in the US alone. The delayed endothelialization of the artery following percutaneous interventions can predispose to acute thrombosis, while the associated injury leads to neo-intimal hyperplasia, both linked to significant clinical events. We are proposing a novel way of addressing this problem by employing endoluminal cellular paving of the stented surface with cells capable of regenerating functional endothelium. To achieve this we are harnessing on the physics of acoustic radiation force, which essentially states that compressible objects in an ultrasound field are displaced away from the energy source due to absorption of the sound wave momentum. This effect is particularly strong with gas-filled lipid microbubbles used as ultrasound contrast agents. By coating the progenitor cells with microbubbles, which can act as the driving engine, the cells can be forced to marginalize and interact with the injured arterial surface when passing by a centrally placed intravascular US catheter. We have a substantial in vitro and in vivo body of data demonstrating the feasibility of the concept for vascular endoluminal cell painting. The current methods for vascular cell seeding require prolonged period of flow cessation, a problem that our current approach minimizes. In collaboration with a multidisciplinary team at the Center for Ultrasound Molecular Imaging and Therapeutics at University of Pittsburgh we will test the therapeutic efficacy of this idea in a step wise fashion testing both autologous endothelial progenitor cells (EPC) and allogeneic mesenchymal stem cells (MSCs), and using electrostatic interaction for cell:bubble association. Under Specific Aim 1, we will define the optimal conditions for delivery of cells to the wall of a vascular phantom in terms of flow conditions, optimal microbubble coating and ultrasound parameters. Potential detrimental effects of the microbubbles and/or ultrasound on cell viability will be tested as well Using an existing FDA approved ultrasound catheter, we will then translate this approach under Specific Aim 2 to a rabbit model of arterial injury, and test the efficacy of each cell in promoting re-endothelialization and using the 2 different types. Again, the safety of the ultrasound delivery in vivo will be specifically addressed. If successful, these translational experiments could represent the basis developing clinically relevant strategies for accelerated re-endothelialization of coronary stents.

抽象的 冠状动脉支架代表可用于治疗症状的武术中的重要工具 动脉粥样硬化的斑块，仅在美国，每年都有超过100万个手术。延迟 经皮干预后，动脉内皮化可能易于急性血栓形成，而 相关的损伤导致新直发增生，都与重大临床事件有关。我们是 提出一种新颖的方法来解决此问题的方法 表面具有能够再生功能性内皮的细胞。为了实现这一目标，我们正在利用 声学辐射力的物理学，本质上指出超声场中的可压缩物体是 由于声波动量的吸收，远离能源。这种效果是 用作超声对比剂的充气脂质微泡特别强。通过涂覆 带有微泡的祖细胞，可以充当驾驶发动机，可以被迫边缘化细胞 并与受伤的动脉表面相互作用，通过中心放置的血管内美国导管。 我们拥有大量的体外和体内数据体，证明了该概念对血管的可行性 内部细胞绘画。当前的血管细胞播种方法需要延长流动周期 停止，我们当前方法最小化的问题。与一个多学科团队合作 匹兹堡大学的超声分子成像和治疗中心我们将测试 该想法的治疗功效在一个逐步的方式测试两个自体内皮祖细胞中 （EPC）和同种异体间充质干细胞（MSC），以及使用静电相互作用：气泡 协会。在特定的目标1下，我们将定义将细胞传递到A壁的最佳条件 在流动条件，最佳微泡涂层和超声参数方面，血管幻影。 还将测试微泡和/或超声对细胞活力的潜在有害影响 使用现有的FDA批准的超声导管，我们将在特定目标2下翻译此方法2 进行动脉损伤的兔模型，并测试每个细胞在促进重新皮层化和 使用两种不同类型。同样，将专门解决体内超声输送的安全性。如果 成功，这些翻译实验可以代表开发临床相关策略的基础 用于加速冠状动脉支架的重新皮层化。