Chachques Juan C
Department of Cardiovascular Surgery, Pompidou Hospital, 20 rue Leblanc, 75015 Paris, France.
Expert Rev Cardiovasc Ther. 2009 Aug;7(8):911-9. doi: 10.1586/erc.09.84.
Cell-based myocardial regenerative therapy is undergoing experimental and clinical trials in order to limit the consequences of decreased contractile function and compliance of damaged ventricles owing to ischemic and nonischemic myocardial diseases. A variety of myogenic and angiogenic cell types have been proposed, such as skeletal myoblasts, mononuclear and mesenchymal bone marrow cells, circulating blood-derived progenitors, adipose-derived stromal cells, induced pluripotent stem cells, umbilical cord cells, endometrial mesenchymal stem cells, adult testis pluripotent stem cells and embryonic cells. Current indications for stem cell therapy concern patients who have had a left- or right-ventricular infarction or idiopathic dilated cardiomyopathies. Other indications and potential applications include patients with diabetic cardiomyopathy, Chagas heart disease (American trypanosomiasis), ischemic mitral regurgitation, left ventricular noncompacted myocardium and pediatric cardiomyopathy. Suitable sources of cells for cardiac implant will depend on the types of diseases to be treated. For acute myocardial infarction, a cell that reduces myocardial necrosis and augments vascular blood flow will be desirable. For heart failure, cells that replace or promote myogenesis, reverse apoptopic mechanisms and reactivate dormant cell processes will be useful. It is important to note that stem cells are not an alternative to heart transplantation; selected patients should be in an early stage of heart failure as the goal of this regenerative approach is to avoid or delay organ transplantation. Since the cell niche provides crucial support needed for stem cell maintenance, the most interesting and realistic perspectives include the association of intramyocardial cell transplantation with tissue-engineered scaffolds and multisite cardiac pacing in order to transform a passive regenerative approach into a 'dynamic cellular support', a promising method for the creation of 'bioartificial myocardium'.
基于细胞的心肌再生疗法正在进行实验和临床试验,以限制由于缺血性和非缺血性心肌疾病导致的受损心室收缩功能下降和顺应性降低的后果。已经提出了多种肌源性和血管生成性细胞类型,如骨骼肌成肌细胞、单核和间充质骨髓细胞、循环血源祖细胞、脂肪来源的基质细胞、诱导多能干细胞、脐带细胞、子宫内膜间充质干细胞、成年睾丸多能干细胞和胚胎细胞。目前干细胞治疗的适应症涉及患有左心室或右心室梗死或特发性扩张型心肌病的患者。其他适应症和潜在应用包括糖尿病性心肌病、恰加斯心脏病(美洲锥虫病)、缺血性二尖瓣反流、左心室心肌致密化不全和小儿心肌病患者。适合心脏植入的细胞来源将取决于待治疗疾病的类型。对于急性心肌梗死,需要一种能减少心肌坏死并增加血管血流量的细胞。对于心力衰竭,能替代或促进肌生成、逆转凋亡机制并重新激活休眠细胞过程的细胞将很有用。需要注意的是,干细胞并非心脏移植的替代品;选定的患者应处于心力衰竭的早期阶段,因为这种再生方法的目标是避免或延迟器官移植。由于细胞龛为干细胞维持提供关键支持,最有趣和现实的前景包括心肌内细胞移植与组织工程支架以及多部位心脏起搏相结合,以便将被动再生方法转变为“动态细胞支持”,这是一种创建“生物人工心肌”的有前景的方法。