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: 9167105
• 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/9167105
• 关键词: Address; Animal Model; Animals; Asses; Autologous; Award; Bathing; Bioinformatics; Biomedical Engineering; Biomedical Research; Bioreactors; Blood Vessels; Cardiac; Cardiac Myocytes; Cardiovascular Surgical Procedures; Cardiovascular system; Cell Communication; Cell Culture Techniques; Cell Transplants; Cells; 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; Life; 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; 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 应聘者拥有医学博士学位，擅长普通外科和血管外科；她拥有公认的 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。候选人的直接目标是让她专注于 工程心脏组织作为物种特异性3D平台的应用和改进努力 确定潜在的心脏治疗药物，长期目标是获得独立的研究人员 在生物医学研究中结合干细胞和组织工程技术开发新型 心血管治疗。为了做到这一点，候选人和她的指导团队精心设计了一个为期5年的 以建立基本知识为目标的协同职业发展计划和研究战略， 在生物医学研究中过渡到终身教职的技能和经验。 相关的个性化研究职业培训计划建立在候选人的高级 具有工程心脏组织、干细胞和外科专业知识的经验，同时解决特定的差距 在生物医学技术和专业技能方面。主要导师是凯文·科斯塔博士， 西奈山伊坎医学院心血管细胞和组织工程(ISMMS)，其 心肌细胞和组织机械生物学研究的综合生物工程方法对于 明确的目标。共同导师罗杰·哈贾尔博士是心血管研究中心(CVRC)的主任 和ISMMS的Arthur和Janet C.Ross医学教授；他补充和加强了 具有世界知名的心血管翻译研究和指导专业知识的培训计划 非常适合指导应聘者的职业发展轨迹。位于西奈山的CVRC提供了丰富的 研究人员发展的环境，以促进生产力并满足特定的 目标。职业发展计划侧重于三个层次的方法：1)来自多学科的指导 一批经验丰富的教师和针对候选人量身定做的教学计划，2)获得专业人员 生存技能和3)有组织地过渡到独立的计划。 该奖项的研究目的是检验一种假说，即来自间充质干细胞的外体 细胞和心脏祖细胞介导旁分泌作用增强心功能 受伤。人类工程心脏组织将首次用于测试这些外切体的效果 生物控制环境中的特定物种模型。测试也将在体内进行，以 对体外研究结果的适用性进行评估。最后，外切体将被加工成microRNA。 微阵列以确定可能提供干细胞治疗好处的潜在候选治疗方案，同时 避免使用活的生物制品，转向更有效和更安全的心脏损伤治疗方法。