Molecular Mechanisms of Stem Cell Engraftment

干细胞移植的分子机制

基本信息

批准号：
8117027
负责人：
CLAUDIA OLIVEIRA RODRIGUES
金额：
$ 13.28万
依托单位：
UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-08-01 至 2015-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8117027
关键词：
Address Adhesions Adult Affect American Anoikis Area Atomic Force Microscopy Attention Binding Bioluminescence Cardiac Cardiovascular Diseases Cause of Death Cell Adhesion Cell Death Cell Proliferation Cell Survival Cell Therapy Cell Transplantation Cell physiology Cell surface Cell-Matrix Junction Cells Chronic Disease Clinical Clinical Research Coronary Arteriosclerosis Country Development Diabetes Mellitus Diagnosis Disease Echocardiography Engraftment Environment Extracellular Matrix Extracellular Matrix Proteins Failure Goals Grant Heart failure Hypertension Hypoxia Immunohistochemistry Infarction Integrins Lead Lentivirus Vector Link Mediating Molecular Myocardial Myocardial Infarction Myocardial Ischemia Myocardial tissue Myocardium Natural regeneration Operative Surgical Procedures Physiological Process Proteins Role Smooth Muscle Stem cell transplant Stem cells Subfamily lentivirinae Testing Therapeutic Tissues Transplantation Up-Regulation Work Wound Healing abstracting cell behavior cell type extracellular functional outcomes genetic manipulation genetically modified cells heart function improved in vivo insight migration mouse model overexpression pressure prevent public health relevance stem cell therapy therapy design therapy development tissue regeneration

项目摘要

DESCRIPTION (provided by applicant): Heart failure is the leading cause of death in Western countries. It has been estimated that approximately 80 million American adults (1 in 3) have one or more forms of cardiovascular disease (CVD). Long-term survival after diagnosis remains poor despite recent improvements in pharmacological and surgical therapy, and development of new forms of treatment is urgently needed. Clinical studies have suggested the potential use of cell-based therapy in the treatment of CVD. However, current clinical results are inconsistent and demonstrated modest benefits. One leading issue that requires experimental attention is poor survival of injected cells. Elucidation of the mechanisms involved in stem cell death and development of new ways to prevent it upon transplantation is essential to maximize the cardioprotective and therapeutic potential of any stem cell type. Our long-term goal is to define new ways to improve stem cell retention and engraftment in the myocardium after transplantation, what can lead to increased myocardium regeneration. One of the first steps that occur after transplantation involves cell adhesion to the tissue extracellular matrix. This interaction is mediated by proteins localized on the cell surface known as integrins. In this proposal, we will test if specific integrins can enhance cardiac stem cell attachment to the myocardium extracellular matrix when overexpressed, and improve myocardium regeneration and function. Our proposed aims will advance understanding of stem cell engraftment in ischemic myocardium and allow direct determination of the link between enhanced engraftment and functional outcome of cell therapy. Insights developed from this grant could provide a significant translational advance in the new area of cell-based therapy. PUBLIC HEALTH RELEVANCE: Heart failure is the leading cause of death from cardiovascular diseases and is the end result of a number of chronic illnesses, including hypertension, diabetes, and coronary artery disease. Long-term survival after diagnosis remains poor despite recent improvements in pharmacological and surgical therapy, and development of new forms of treatment, such as stem cell therapy, is urgently needed. (End of Abstract)

描述（由申请人提供）：心力衰竭是西方国家死亡的主要原因。据估计，大约 8000 万美国成年人（三分之一）患有一种或多种心血管疾病 (CVD)。尽管最近在药物和手术治疗方面取得了进展，但诊断后的长期生存率仍然很差，因此迫切需要开发新的治疗形式。临床研究表明细胞疗法在治疗 CVD 中具有潜在用途。然而，目前的临床结果并不一致，并且显示出有限的益处。需要实验注意的一个主要问题是注射细胞的存活率低。阐明干细胞死亡的机制和开发移植后预防干细胞死亡的新方法对于最大限度地发挥任何干细胞类型的心脏保护和治疗潜力至关重要。我们的长期目标是确定新的方法来改善移植后心肌中干细胞的保留和植入，从而增加心肌再生。移植后发生的第一步涉及细胞粘附到组织细胞外基质。这种相互作用是由位于细胞表面的称为整合素的蛋白质介导的。在本提案中，我们将测试特定的整合素在过度表达时是否可以增强心脏干细胞与心肌细胞外基质的附着，并改善心肌的再生和功能。我们提出的目标将促进对缺血心肌中干细胞植入的理解，并允许直接确定增强植入与细胞治疗的功能结果之间的联系。从这笔资助中得出的见解可以为基于细胞的治疗新领域提供重大的转化进展。公共卫生相关性：心力衰竭是心血管疾病死亡的主要原因，也是许多慢性疾病（包括高血压、糖尿病和冠状动脉疾病）的最终结果。尽管最近药物和手术治疗取得了进展，但诊断后的长期生存率仍然很差，并且迫切需要开发新的治疗形式，例如干细胞疗法。（摘要完）