CPC Excosomes for Cardiac Therapy

用于心脏治疗的 CPC 外泌体

• 批准号: 8903585
• 负责人: Michael E Davis
• 金额: $ 43.57万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2016-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8903585
• 关键词: Adult; Affect; Age; Allogenic; Autologous; Biocompatible Materials; Biodistribution; Biological Assay; Biological Markers; Blood; Cardiac; Cardiac Myocytes; Cardiovascular Diseases; Cell Therapy; Cell Transplantation; Cell physiology; Cells; Child; Chronic; Clinical Trials; Collaborations; Computer Analysis; Data; Disease; Endothelial Cells; Epigenetic Process; Exposure to; Extracellular Space; Fibroblasts; Fibrosis; Gender; Gene Expression; Gene Expression Regulation; Growth Factor; Healed; Health; Healthcare; Heart failure; Human; Hypoxia; Individual; Infarction; Injection of therapeutic agent; Ischemia; Label; Least-Squares Analysis; Lipoproteins; Measures; Mechanics; Mediating; Mesenchymal Stem Cells; Methods; MicroRNAs; Modeling; Molecular Profiling; Morbidity - disease rate; Multivariate Analysis; Myocardial Infarction; Myocardium; Natural regeneration; Newborn Infant; Operative Surgical Procedures; Outcome; Output; Patients; Pattern; Proto-Oncogene Protein c-kit; Publishing; Rattus; Regression Analysis; Reperfusion Injury; Reperfusion Therapy; Role; Sampling; Speed; Stem cells; Surgeon; System; Testing; Therapeutic; Tissues; Toddler; Tube; age effect; age group; angiogenesis; base; cardiac repair; cell type; early childhood; effective therapy; extracellular; functional improvement; gene therapy; healing; hemodynamics; horizontal cell; immunogenicity; imprint; improved; improved functioning; in vivo; in vivo imaging; meetings; mortality; paracrine; prevent; regenerative; repaired; residence; response; stem

DESCRIPTION (provided by applicant): Adverse remodeling of the myocardium after myocardial infarction speeds progression to heart failure. While cell therapy has been met with great enthusiasm, there are numerous shortcomings that prevent long-term functional improvements. Moreover, these cells come from diseased individuals and immunogenicity limits most studies to autologous therapy. Finally, it is widely believed that the main effect of cell therapy is mediated by paracrine effectors and not the cells themselves. We have isolated rat and human cardiac progenitor cells that are cardiac-derived, express c-kit, do not express any markers of cardiogenic lineage, but can differentiate in to all cardiac cell types. These cells basally release microRNA (miR) in to the extracellular space. When treated with hypoxic conditions, these cells increase cardioprotective miRs within exosomes. Preliminary studies demonstrate that these hypoxic exosomes enhance endothelial cell tube formation and decrease fibrotic gene expression in fibroblasts. Therefore, the objective of this proposal is to examine the protective/regenerative capacity of these exosomes in rat models of ischemia-reperfusion. Additionally, with a large number of patient samples from children and adults, we can perform multivariate analysis to examine the factors that affect various in vivo mechanisms. Factors include patient age, gender, and exposure to hypoxic conditions. Completion of the proposed studies will determine whether hypoxic exosomes are a beneficial therapy for ischemia-reperfusion injury, as well as determine potential patient factors that contribute to these responses.

描述（由申请人提供）：心肌梗塞后心肌的不良重塑加速了心力衰竭的进展。尽管细胞疗法受到了极大的热情，但它仍然存在许多缺点，阻碍了长期的功能改善。此外，这些细胞来自患病个体，免疫原性限制了大多数自体治疗的研究。最后，人们普遍认为细胞疗法的主要作用是由旁分泌效应器介导的，而不是细胞本身。 我们分离出大鼠和人类心脏祖细胞，它们源自心脏，表达 c-kit，不表达任何心源性谱系标记，但可以分化为所有心脏细胞类型。这些细胞基本上将 microRNA (miR) 释放到细胞外空间。当在缺氧条件下处理时，这些细胞会增加外泌​​体内的心脏保护性 miR。初步研究表明，这些缺氧外泌体可增强内皮细胞管的形成并减少成纤维细胞中的纤维化基因表达。因此，该提案的目的是检查这些外泌体在缺血再灌注大鼠模型中的保护/再生能力。此外，通过大量来自儿童和成人的患者样本，我们可以进行多变量分析来检查影响各种体内机制的因素。因素包括患者年龄、性别和是否处于缺氧条件下。 完成拟议的研究将确定缺氧外泌体是否是缺血再灌注损伤的有益疗法，并确定有助于这些反应的潜在患者因素。