Stem Cell Therapy and Postinfarction LV Remodeling

干细胞治疗和梗死后左室重塑

• 批准号: 6361149
• 负责人: Jianyi Zhang
• 金额: $ 37.13万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-24 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6361149
• 关键词: bioenergetics; cardiac myocytes; cell differentiation; congestive heart failure; heart function; heart metabolism; magnetic resonance imaging; myocardial infarction; nonhuman therapy evaluation; nuclear magnetic resonance spectroscopy; regeneration; stem cell transplantation; stem cells; swine

DESCRIPTION (provided by applicant): After a period of stable postinfarction left ventricular (LV) remodeling, progressive myocardial dysfunction can develop that ultimately leads to overt congestive heart failure (CHF). The present therapeutic options for post infarction LV remodeling and heart failure are limited. Although cardiomyocytes lose the capability to proliferate after birth, several exciting recently published studies have shown that tissue specific stem cells may have the ability to generate cells of tissues from unrelated organs. The primary focus of the current proposal is to examine whether a small population of multipotent stem cells persists in post-natal tissues, and whether these stem cells can be used to treat myocardial infarct. These studies will use a swine model of postinfarction LV remodeling in which about 30 percent of the animals develop CHF within 8 weeks after coronary artery occlusion. Studies will determine whether stem cell transplantation can prevent infarct expansion and aneurysm formation or prevent the transition to heart failure. The effect of stem cell transplant on energy metabolism will also be examined. Following myocardial infarction longitudinal closed chest studies will measure LV mass and volume, ejection fraction and wall stress with magnetic resonance (MR) imaging, while myocardial ATP, creatine phosphate (CP), inorganic phosphate (Pi), and the regulation of oxidative phosphorylation will be examined with 31P-MR spectroscopy. To examine the potential for stem cell proliferation and differentiation in an ischemic environment, stem cells will be transferred into the coronary bed distal to a left anterior descending coronary artery (or a left circumflex coronary artery) occlusion. To test whether the beneficial effects are greater when the cells are transplanted as differentiated myocytes, stem cells will be predifferentiated to myocytes in culture and then transferred into the infarct. To determine whether cell transplantation is more beneficial in the presence of an open infarct-related coronary artery, cells will be transplanted into the infarcted myocardium when the coronary is opened after infarct has been produced by 24 hours of occlusion. By providing insight into the feasibility of stem cell transplantation, the results may lead to new treatments for LV ischemic injury or failure.

描述（由申请人提供）：经过一段稳定的梗死后 左心室（LV）重构、进行性心肌功能障碍可 最终导致明显的充血性心力衰竭（CHF）。的 为梗死后LV重塑和心力衰竭提供治疗选择 是有限的。尽管心肌细胞在心肌缺血后失去了增殖能力， 最近发表的几项令人兴奋的研究表明， 特定的干细胞可以具有从细胞中产生组织细胞的能力， 无关器官当前提案的主要重点是审查 一小群多能干细胞是否在出生后持续存在， 组织，以及这些干细胞是否可用于治疗心肌梗死。 这些研究将使用梗死后LV重构的猪模型， 大约30%的动物在冠状动脉造影后8周内发生CHF， 动脉闭塞研究将确定干细胞移植是否可以 防止梗塞扩大和动脉瘤形成，或防止过渡到 心衰干细胞移植对能量代谢的影响将 也要检查。心肌梗死后纵行闭胸 研究将测量LV质量和体积、射血分数和室壁应力， 磁共振（MR）成像，而心肌ATP，磷酸肌酸（CP）， 无机磷酸盐（Pi），氧化磷酸化的调节将 用31 P-MR光谱进行检查。研究干细胞的潜力 在缺血环境中的增殖和分化，干细胞将 转移到左前降支远端的冠状动脉床 冠状动脉（或左回旋支冠状动脉）闭塞。测试 当细胞被移植时， 干细胞在分化的肌细胞中将预分化为肌细胞， 培养，然后转移到梗死区。确定单元格是否 移植在存在开放性梗死相关的 冠状动脉，细胞将被移植到梗死心肌， 冠状动脉在梗塞形成24小时后开放， 闭塞通过深入了解干细胞的可行性， 移植，结果可能导致新的治疗左室缺血性损伤 或者失败