Harnessing the Benefits of Adult Stem Cell Exosomes for Enhancing Cardiac Contractile Function

利用成体干细胞外泌体的益处增强心脏收缩功能

基本信息

批准号：
9750784
负责人：
Irene Cal y Mayor-Turnbull
金额：
$ 14.02万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-08-01 至 2021-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9750784
关键词：
3-Dimensional Address Animal Model Animals Asses Autologous Award Bathing Bioinformatics Biological Biomedical Engineering Biomedical Research Bioreactors Blood Vessels Cardiac Cardiac Myocytes Cardiovascular system Cell Communication Cell Culture Techniques Cell Transplantation Cell Transplants Cells Clinical Clinical Trials Complement Controlled Environment Culture Media Custom Data Development Development Plans Echocardiography Environment Faculty Foundations Goals Heart Injuries Human Human Engineering In Vitro Injury Intervention Journals Knowledge Lead Measurement Measures Mediating Medicine Mentors Mentorship Mesenchymal Stem Cells MicroRNAs Modeling Monitor Myocardial Myocardial Infarction Myocardium Nude Rats Operative Surgical Procedures Paracrine Communication Performance Positioning Attribute Process Productivity Proto-Oncogene Protein c-kit Publications Recovery Research Research Personnel Risk Sampling Signal Transduction Source Stem cell transplant Stem cells Structure Systems Biology Techniques Testing Therapeutic Therapeutic Agents Time Tissue Engineering Tissues Training Training Programs Translational Research United States National Institutes of Health adult stem cell cardiac repair cardiac tissue engineering career career development cell type cellular engineering clinically relevant design exosome experience functional outcomes heart function human stem cells improved in vitro Model in vivo induced pluripotent stem cell injured injury and repair male medical schools medical specialties multidisciplinary nanotherapy novel novel therapeutics paracrine professor programs repaired research and development scale up skills stem cell therapy technology development tenure track therapeutic candidate treatment strategy

项目摘要

Project Summary The candidate holds an MD with specialty in General Surgery and Vascular Surgery; she has a proven track record of research productivity and publications in leading journals in the fields of Vascular Surgery, Cardiovascular Medicine, and Tissue Engineering. The candidate's immediate objectives are to focus her efforts on the application and improvement of engineered cardiac tissues as a species-specific 3D platform to identify potential cardiotherapeutic agents, with the long-term goal of gaining independence as an investigator in biomedical research combining stem cell and tissue engineering technologies for the development of novel cardiovascular therapies. To accomplish this, the candidate and her mentoring team have crafted a 5-year synergistic career development plan and research strategy with the goal of establishing essential knowledge, skills and experience to transition to a tenure-track faculty position in biomedical research. The associated individualized research career training plan builds on the candidate's advanced experience with engineered cardiac tissues, stem cells, and surgical expertise, while addressing specific gaps in biomedical techniques and professional skills. The primary mentor is Dr. Kevin Costa, Director of Cardiovascular Cell and Tissue Engineering at the Icahn School of Medicine at Mount Sinai (ISMMS), whose integrated bioengineering approach to cardiac cell and tissue mechanobiology research is essential to the Specific Aims. The co-mentor, Dr. Roger Hajjar, is Director of the Cardiovascular Research Center (CVRC) and the Arthur and Janet C. Ross Professor of Medicine at ISMMS; he complements and enhances the training plan with world renowned expertise in cardiovascular translational research and mentorship which is ideally suited to guide the candidate's career development trajectory. The CVRC at Mount Sinai offers a rich environment for researcher development to facilitate productivity and cover all requirements of the Specific Aims. The career development plan focuses on a 3-tiered approach: 1) mentorship from a multidisciplinary group of experienced faculty and a candidate-specific tailored didactic program, 2) acquisition of professional survival skills and 3) a plan for structured transition to independence. The research objective of this award is to test the hypothesis that exosomes from mesenchymal stem cells as well as cardiac progenitor cells mediate the paracrine effects on enhancement of cardiac function after injury. Human engineered cardiac tissues will be used to test the effects of these exosomes for the first time on a species-specific model in a biologically controlled environment. Testing will also be conducted in vivo for assessment of the applicability of the in vitro findings. Lastly, exosomes will be processed for microRNA microarray to identify potential therapeutic candidates that may provide the benefits of stem cell therapy while circumventing the administration of live biologics, towards more effective and safer therapies for cardiac injury.

项目概要候选人拥有普通外科和血管外科专业医学博士学位；她有一个被证明的血管外科领域领先期刊的研究成果和出版物的跟踪记录，心血管医学和组织工程。候选人的近期目标是集中精力致力于应用和改进工程心脏组织作为物种特异性 3D 平台识别潜在的心脏治疗药物，长期目标是获得独立的研究者身份生物医学研究结合干细胞和组织工程技术来开发新的心血管治疗。为了实现这一目标，候选人和她的指导团队制定了一个为期 5 年的计划以建立必要知识为目标的协同职业发展计划和研究策略，过渡到生物医学研究终身教职的技能和经验。相关的个性化研究职业培训计划以候选人的先进水平为基础拥有工程心脏组织、干细胞和外科专业知识方面的经验，同时解决特定的差距生物医学技术和专业技能。主要导师是Kevin Costa博士，西奈山伊坎医学院 (ISMMS) 的心血管细胞和组织工程，心脏细胞和组织力学生物学研究的综合生物工程方法对于心脏细胞和组织力学生物学研究至关重要具体目标。共同导师 Roger Hajjar 博士是心血管研究中心 (CVRC) 主任以及 ISMMS 的 Arthur 和 Janet C. Ross 医学教授；他补充并增强了具有世界知名的心血管转化研究和指导专业知识的培训计划非常适合指导候选人的职业发展轨迹。西奈山的 CVRC 提供丰富的为研究人员发展提供环境，以提高生产力并满足特定领域的所有要求目标。职业发展计划侧重于三层方法：1）来自多学科的指导一群经验丰富的教师和针对候选人的量身定制的教学计划，2）获得专业知识生存技能和 3) 结构化过渡到独立的计划。该奖项的研究目的是检验来自间充质干细胞的外泌体的假设细胞以及心脏祖细胞介导旁分泌作用，增强心脏功能受伤。人类工程心脏组织将首次用于测试这些外泌体对心脏的影响生物控制环境中的物种特异性模型。还将进行体内测试评估体外研究结果的适用性。最后，外泌体将被加工为 microRNA 微阵列来识别潜在的治疗候选者，这些候选者可以提供干细胞治疗的益处，同时规避活生物制剂的使用，寻求更有效、更安全的心脏损伤治疗方法。