Stem cell therapy as a treatment option for acute myocardial infarction or heart failure caused by ischemic or nonischemic cardiomyopathy has focused on direct cardiac delivery of stem cells to facilitate cardiac engraftment. Once engrafted, it was believed that these cells would either transdifferentiate into new functioning myocytes or stimulate the expansion of resident myocardial stem cells. However, a sea change in thinking about cell therapy in cardiovascular disease has occurred as mounting evidence indicates that (1) inflammation is a major mechanism contributing to the progressive myocardial dysfunction seen in patients post-acute myocardial infarction and in patients with cardiomyopathy, and (2) systemic paracrine-mediated anti-inflammatory effects of stem cells can drive beneficial cardiac effects in these diseases. These concepts lead to a potentially transformative strategy that intravenous delivery of stem cells, through systemic anti-inflammatory mechanisms, improves myocardial function and thereby obviates the need for invasive methods of stem cell delivery. Until recently, the prevailing view of the mechanism responsible for any potential benefit of stem cells in patients with acute myocardial infarction (AMI) or with heart failure (HF) caused by ischemic or nonischemic cardiomyopathy (ICM/NICM) was that benefit derived from local effects—once engrafted in damaged myocardium, the stem cells either transdifferentiate into functional myocardium, stimulate resident myocardial stem cells to expand, and repopulate the heart with functioning myocytes or secrete substances leading to myocardial healing. This mechanistic perspective implied that the greater the number of engrafted cells in the myocardium, the greater the cardiac benefit. Because few intravenously administered stem cells engraft in injured myocardium, invasive strategies providing direct delivery of stem cells to the heart were uniformly adopted. This necessarily involved either catheter-based delivery (intracoronary or transendocardial injection) or surgical delivery (direct intramyocardial injection). A transformative concept relating to stem cell treatment of patients with AMI or ICM/NICM has recently …

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旁分泌介导的间充质干细胞的全身抗炎活性

干细胞疗法作为由缺血性或非缺血性心肌病引起的急性心肌梗塞或心力衰竭的治疗选择，已集中于直接向心脏递送干细胞以促进心脏植入。一旦植入，人们相信这些细胞将转分化为新的功能性心肌细胞或刺激驻留的心肌干细胞的扩增。但是，关于心血管疾病中细胞疗法的思考发生了巨大变化，因为越来越多的证据表明，（1）炎症是导致急性心肌梗死后和心肌病患者中进行性心肌功能障碍的主要机制，并且（ 2）全身旁分泌介导的干细胞抗炎作用可以驱动这些疾病的有益心脏作用。这些概念导致了潜在的变革性策略，即通过全身抗炎机制静脉内输送干细胞改善了心肌功能，从而消除了对干细胞输送的侵入性方法的需求。直到最近，对由缺血性或非缺血性心肌病（ICM / NICM）引起的急性心肌梗死（AMI）或心力衰竭（HF）患者干细胞可能产生任何潜在益处的机制的普遍看法是，这种益处源自局部作用-一旦植入受损的心肌中，干细胞就会转分化为功能性心肌，刺激驻留的心肌干细胞扩增，并通过功能性心肌细胞或分泌导致心肌愈合的物质重新填充心脏。这种机械观点表明，心肌中植入的细胞数量越多，对心脏的益处就越大。由于很少有静脉内施用的干细胞移植到受损的心肌中，因此统一采用了将干细胞直接递送至心脏的侵入性策略。这必然涉及基于导管的分娩（冠状动脉内或心内膜内注射）或手术分娩（直接心肌内注射）。与AMI或ICM / NICM患者的干细胞治疗有关的一种变革性概念最近… 这必然涉及基于导管的分娩（冠状动脉内或心内膜内注射）或手术分娩（直接心肌内注射）。与AMI或ICM / NICM患者的干细胞治疗有关的一种变革性概念最近… 这必然涉及基于导管的分娩（冠状动脉内或心内膜内注射）或手术分娩（直接心肌内注射）。与AMI或ICM / NICM患者的干细胞治疗有关的一种变革性概念最近…