Department of Pathology and Lab Medicine, University of Cincinnati, Cincinnati, Ohio 45267, USA.
Mol Pharm. 2011 Oct 3;8(5):1446-57. doi: 10.1021/mp2001318. Epub 2011 Jun 8.
The conventional treatment modalities for ischemic heart disease only provide symptomatic relief to the patient without repairing and regenerating the damaged myocardium. Stem cell transplantation has emerged as a promising alternative therapeutic approach for cardiovascular diseases. Stem cells possess the potential of differentiation to adopt morphofunctional cardiac and vasculogenic phenotypes to repopulate the scar tissue and restore regional blood flow in the ischemic myocardium. These beneficial therapeutic effects make stem cell transplantation the method of choice for the treatment of ischemic heart disease. The efficacy of stem cell transplantation may be augmented by genetic manipulation of the cells prior to transplantation. Not only will insertion of therapeutic transgene(s) into the stem cells support the survival and differentiation of cells in the unfavorable microenvironment of the ischemic myocardium, but also the genetically manipulated stem cells will serve as a source of the transgene expression product in the heart for therapeutic benefits. We provide an overview of the extensively studied stem cell types for cardiac regeneration, the various methods in which these cells have been genetically manipulated and rationale of genetic modification of stem cells for use in regenerative cardiovascular therapeutics.
缺血性心脏病的传统治疗方法仅为患者提供症状缓解,而不能修复和再生受损的心肌。干细胞移植已成为心血管疾病有前途的治疗方法。干细胞具有分化为具有心脏形态和血管生成表型的细胞的潜力,以重新填充疤痕组织并恢复缺血心肌中的局部血流。这些有益的治疗效果使干细胞移植成为治疗缺血性心脏病的首选方法。在移植前对细胞进行基因操作可以增强干细胞移植的疗效。将治疗性转基因(s)插入干细胞中,不仅可以支持细胞在缺血心肌不利的微环境中的存活和分化,而且经过基因修饰的干细胞还可以作为心脏中转基因表达产物的来源,从而带来治疗益处。我们概述了广泛研究的用于心脏再生的干细胞类型,这些细胞已通过多种方法进行了基因操作,以及用于再生心血管治疗的干细胞基因修饰的原理。