Neuroscience and Neuroengineering Center, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
Curr Drug Targets. 2013 Jan 1;14(1):81-9. doi: 10.2174/138945013804806497.
Ischemic stroke is one of the leading causes of death and disability worldwide. There is no effective treatment for ischemic stroke apart from thrombolytic therapy, which has a narrow therapeutic time window. Gene therapy has proven to be effective in experimental stroke, but it suffers from disadvantages that limit its clinical application, such as difficulty in intracranial delivering of therapeutic genes, low efficacy in transfecting host cells and long-term expression of exogenous genes. Delivering therapeutic genes to the ischemic brain via stem cells is an alternative strategy of combined gene and stem cell therapy. There are advantages for stem cell-mediated gene delivery as opposed to direct gene transfer. In recent years, studies used stem cells that over-express different neurotrophic factors, such as BDNF, GDNT, or NT3, and found that the delivery of these genetically-modified stem cells to animal models of ischemic stroke is safe and effective, thus suggesting that stem cell-based gene therapy may be a promising treatment for stroke. This review summarizes the advantages and recent progress of stem cell-based gene therapy for ischemic stroke. We also discuss the relevant strategy for optimizing stem cell-based gene therapy and discuss the potential strategies for its future application.
缺血性脑卒中是全球范围内导致死亡和残疾的主要原因之一。除了溶栓治疗外，目前尚无有效的治疗方法，但溶栓治疗的治疗时间窗较窄。基因治疗已被证明在实验性脑卒中中有疗效，但它存在一些限制其临床应用的缺点，如难以将治疗基因递送至颅内、宿主细胞转染效率低和外源基因的长期表达等。通过干细胞将治疗基因递送至缺血性大脑是一种联合基因和干细胞治疗的替代策略。与直接基因转移相比，干细胞介导的基因传递具有优势。近年来，研究使用过表达不同神经营养因子（如 BDNF、GDNF 或 NT3）的干细胞，并发现将这些基因修饰的干细胞递送至缺血性脑卒中动物模型是安全有效的，这表明基于干细胞的基因治疗可能是一种有前途的脑卒中治疗方法。本综述总结了基于干细胞的基因治疗缺血性脑卒中的优势和最新进展。我们还讨论了优化基于干细胞的基因治疗的相关策略，并探讨了其未来应用的潜在策略。
