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: 9319796
• 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/9319796
• 关键词: 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 Therapy; Cell Transplants; Cells; Clinical; Clinical Trials; Complement; Controlled Environment; Culture Media; Custom; Data; Development; Development Plans; Echocardiography; Engineering; Environment; Faculty; Foundations; Goals; 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; career; career development; cell type; cellular engineering; clinically relevant; design; exosome; experience; functional outcomes; 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 候选人拥有一家医学博士，并具有一般手术和血管手术的专业；她有一个验证的 在血管手术领域的领先期刊中的研究生产力和出版物的记录， 心血管医学和组织工程。候选人的直接目标是集中她 在应用和改善工程心脏组织作为特定物种的3D平台上的努力 确定潜在的心脏治疗剂，其长期目标是获得独立性作为研究者 在结合干细胞和组织工程技术的生物医学研究中用于开发新型 心血管疗法。为此，候选人和她的指导团队制定了5年 协同的职业发展计划和研究策略，目的是建立基本知识， 在生物医学研究中过渡到终身教师职位的技能和经验。 相关的个性化研究职业培训计划基于候选人的高级 具有工程性心脏组织，干细胞和手术专业知识的经验，同时解决特定差距 在生物医学技术和专业技能中。主要导师是凯文·科斯塔（Kevin Costa）博士 西奈山（ISMMS）的伊坎医学院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对于 具体目标。联合学者Roger Hajjar博士是心血管研究中心（CVRC）的主任 以及ISMM的Arthur和Janet C. Ross医学教授；他补充并增强了 培训计划具有世界著名的心血管转化研究和指导方面的专业知识 非常适合指导候选人的职业发展轨迹。西奈山的CVRC提供了富人 研究人员发展的环境，以促进生产力并满足特定的所有要求 目标。职业发展计划的重点是三层方法：1）来自多学科的指导 一组经验丰富的教师和特定候选人的量身定制的教学计划，2）获取专业人士 生存技巧和3）结构化过渡到独立的计划。 该奖项的研究目的是检验中充质茎外泌体的假设 细胞以及心脏祖细胞介导旁分泌对增强心脏功能的影响 受伤。人类工程性心脏组织将首次用于测试这些外泌体的影响 在生物学控制环境中的物种特异性模型。还将在体内进行测试 评估体外发现的适用性。最后，将为microRNA处理外泌体 微阵列确定可能提供干细胞疗法益处的潜在治疗候选者 规避生物制剂的给药，以更有效，更安全的心脏损伤疗法。