Li Shengwen Calvin, Wang Lang, Jiang Hong, Acevedo Julyana, Chang Anthony Christopher, Loudon William Gunter
Children's Hospital of Orange County Research Institute, CA 92868, USA.
Cell Biol Int. 2009 Mar;33(3):255-67. doi: 10.1016/j.cellbi.2008.11.009. Epub 2008 Dec 3.
Heart disorders are a major health concern worldwide responsible for millions of deaths every year. Among the many disorders of the heart, myocardial infarction, which can lead to the development of congestive heart failure, arrhythmias, or even death, has the most severe social and economic ramifications. Lack of sufficient available donor hearts for heart transplantation, the only currently viable treatment for heart failure other than medical management options (ACE inhibition, beta blockade, use of AICDs, etc.) that improve the survival of patients with heart failure emphasises the need for alternative therapies. One promising alternative replaces cardiac muscle damaged by myocardial infarction with new contractile cardiomyocytes and vessels obtained through stem cell-based regeneration. We report on the state of the art of recovery of cardiac functions by using stem cell engineering. Current research focuses on (a) inducing stem cells into becoming cardiac cells before or after injection into a host, (b) growing replacement heart tissue in vitro, and (c) stimulating the proliferation of the post-mitotic cardiomyocytes in situ. The most promising treatment option for patients is the engineering of new heart tissue that can be implanted into damaged areas. Engineering of cardiac tissue currently employs the use of co-culture of stem cells with scaffold microenvironments engineered to improve tissue survival and enhance differentiation. Growth of heart tissue in vitro using scaffolds, soluble collagen, and cell sheets has unique advantages. To compensate for the loss of ventricular mass and contractility of the injured cardiomyocytes, different stem cell populations have been extensively studied as potential sources of new cells to ameliorate the injured myocardium and eventually restore cardiac function. Unresolved issues including insufficient cell generation survival, growth, and differentiation have led to mixed results in preclinical and clinical studies. Addressing these limitations should ensure the successful production of replacement heart tissue to benefit cardiac patients.
心脏疾病是全球主要的健康问题,每年导致数百万人死亡。在众多心脏疾病中,心肌梗死可导致充血性心力衰竭、心律失常甚至死亡,具有最严重的社会和经济影响。心脏移植是目前除药物治疗方案(如ACE抑制、β受体阻滞剂、使用植入式心律转复除颤器等)之外治疗心力衰竭的唯一可行方法,但可供移植的心脏供体不足,这凸显了替代疗法的必要性。一种有前景的替代方法是通过基于干细胞的再生获得新的收缩性心肌细胞和血管,来替代因心肌梗死受损的心肌。我们报告了利用干细胞工程恢复心脏功能的最新进展。目前的研究集中在:(a)在将干细胞注入宿主之前或之后诱导其分化为心脏细胞;(b)在体外培养替代心脏组织;(c)原位刺激有丝分裂后心肌细胞的增殖。对患者来说,最有前景的治疗选择是构建可植入受损区域的新心脏组织。目前心脏组织工程采用干细胞与经设计以改善组织存活和增强分化的支架微环境共培养的方法。利用支架、可溶性胶原蛋白和细胞片在体外培养心脏组织具有独特优势。为了弥补受损心肌细胞心室质量和收缩力的损失,人们广泛研究了不同的干细胞群体,将其作为新细胞的潜在来源,以改善受损心肌并最终恢复心脏功能。包括细胞生成、存活、生长和分化不足等未解决的问题,导致临床前和临床研究结果参差不齐。解决这些限制应能确保成功生产替代心脏组织,使心脏病患者受益。