Molecular Mechanisms of Stem Cell Engraftment

干细胞移植的分子机制

• 批准号: 8669804
• 负责人: CLAUDIA OLIVEIRA RODRIGUES
• 金额: $ 13.31万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2015-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8669804
• 关键词: Address; Adhesions; Adult; Affect; American; 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; stem cell therapy; therapy design; therapy development; tissue regeneration

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.

描述（由申请人提供）：心力衰竭是西方国家的主要死亡原因。据估计，大约8000万美国成年人（1/3）患有一种或多种形式的心血管疾病（CVD）。诊断后的长期生存率仍然很差，尽管最近在药物和手术治疗的改进，并迫切需要开发新的治疗形式。临床研究表明，以细胞为基础的疗法在治疗CVD中具有潜在的用途。然而，目前的临床结果并不一致，并证明了适度的好处。需要实验关注的一个主要问题是注射细胞的存活率差。阐明干细胞死亡的机制，并开发新的方法来防止移植后的心脏保护和治疗潜力的任何干细胞类型的最大化是必不可少的。我们的长期目标是确定新的方法来改善干细胞移植后在心肌中的保留和植入，从而增加心肌再生。移植后发生的第一个步骤之一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。在这个提议中，我们将测试特定的整合素是否可以增强心脏干细胞在过表达时与心肌细胞外基质的附着，并改善心肌再生和功能。我们提出的目标将促进对缺血心肌干细胞移植的理解，并允许直接确定增强的移植和细胞治疗的功能结果之间的联系。从这笔赠款中获得的见解可以在基于细胞的治疗的新领域提供重大的转化进展。