Angert David, Houser Steven R
Department of Physiology, Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA, USA.
Curr Treat Options Cardiovasc Med. 2009 Aug;11(4):316-27. doi: 10.1007/s11936-009-0032-6.
Heart failure (HF) is a chronic disease and a significant global public health concern. Current medical treatment for HF can reduce symptoms but does little to decrease mortality and the need for cardiac transplantation. Novel therapies are needed to further decrease mortality and limit or eliminate the need for cardiac transplantation. Recently, several basic science and clinical trials have suggested that enhancing endogenous regeneration (repair) and exogenous cell therapy might be an approach to improve the function of the failing heart. This article reviews cell therapy clinical trials in patients with chronic HF. The three major subgroups of cells being studied in phase 1 and beginning phase 2 trials are skeletal myoblasts, bone marrow-derived mononuclear cells, and enriched subpopulations of bone marrow and cardiac stem cells. Techniques for stimulating upregulation of endogenous bone marrow progenitor cells in the circulating blood have raised serious safety issues and need to be carefully evaluated. Intracoronary infusion and both transepicardial and transendocardial direct injection of stem cells have been tested clinically and shown to be safe. Skeletal myoblast implantation has led to improved cardiac function, but studies show formation of skeletal muscle in the heart and a lack of electrical integration with surrounding myocardium, a cause for concern. Bone marrow-derived mononuclear cells and enriched subpopulations of cardiac and bone marrow stem cells have been studied extensively in animals and in recent clinical trials, with both controversy and success. There is still much room for improvement, but animal and human studies of enriched subpopulations of cardiac and bone marrow stem cells have shown that these cells are safe, have significant capability for cardiac repair, and offer the best chance for legitimate medical therapy for patients with chronic HF.
心力衰竭（HF）是一种慢性疾病，也是全球重大的公共卫生问题。目前针对HF的药物治疗可以减轻症状，但对降低死亡率和减少心脏移植需求作用甚微。需要新的治疗方法来进一步降低死亡率，并限制或消除心脏移植的需求。最近，一些基础科学和临床试验表明，增强内源性再生（修复）和外源性细胞治疗可能是改善衰竭心脏功能的一种方法。本文综述了慢性HF患者的细胞治疗临床试验。在1期和开始的2期试验中研究的三大类细胞亚群是骨骼肌成肌细胞、骨髓来源的单个核细胞，以及富集的骨髓和心脏干细胞亚群。刺激循环血液中内源性骨髓祖细胞上调的技术引发了严重的安全问题，需要仔细评估。冠状动脉内输注以及经心外膜和经心内膜直接注射干细胞已在临床上进行了测试，并证明是安全的。骨骼肌成肌细胞植入已导致心脏功能改善，但研究表明心脏中形成了骨骼肌，且与周围心肌缺乏电整合，这令人担忧。骨髓来源的单个核细胞以及富集的心脏和骨髓干细胞亚群已在动物和最近的临床试验中得到广泛研究，既有争议也有成功之处。仍有很大的改进空间，但对富集的心脏和骨髓干细胞亚群的动物和人体研究表明，这些细胞是安全的，具有显著的心脏修复能力，为慢性HF患者提供了合法医学治疗的最佳机会。
