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

• 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
• 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

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.

项目摘要 候选人拥有普通外科和血管外科专业的医学博士学位;她有一个成熟的 在血管外科领域的领先期刊上的研究生产力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让她 致力于工程心脏组织作为物种特异性3D平台的应用和改进， 确定潜在的心脏病药物，长期目标是作为研究者获得独立性 在生物医学研究中，结合干细胞和组织工程技术， 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项为期5年的 协同职业发展计划和研究战略，目标是建立基本知识， 技能和经验，过渡到生物医学研究终身教职。 相关的个性化研究职业培训计划建立在候选人的先进的 工程心脏组织、干细胞和外科专业知识方面的经验，同时解决具体差距 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， 心脏细胞和组织机械生物学研究的综合生物工程方法是必不可少的 具体目标。共同导师Roger Hajjar博士是心血管研究中心（CVRC）主任 还有亚瑟和珍妮特C.罗斯医学教授在ISMMS;他补充和提高了 在心血管转化研究和指导方面拥有世界知名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提供了丰富的 研究人员发展的环境，以促进生产力，并涵盖具体的所有要求 目标。职业发展计划侧重于三个层次的方法：1）来自多学科的导师 一群经验丰富的教师和一个特定的候选人量身定制的教学计划，2）获得专业 生存技能和3）向独立过渡的计划。 该奖项的研究目标是验证来自间充质干细胞的外泌体 细胞以及心脏祖细胞介导的旁分泌作用增强心脏功能后， 损伤人类工程心脏组织将首次用于测试这些外泌体对 在生物控制环境中的物种特异性模型。还将在体内进行试验， 评估体外结果的适用性。最后，外泌体将被加工成microRNA， 微阵列来识别可能提供干细胞治疗益处的潜在治疗候选物， 避免使用活的生物制剂，以实现更有效和更安全的心脏损伤治疗。