Ajou University School of Medicine, Brain Disease Research Center, Institute for Medical Sciences, Suwon, Republic of Korea.
Expert Opin Biol Ther. 2011 Dec;11(12):1599-610. doi: 10.1517/14712598.2011.631908. Epub 2011 Oct 21.
Stem cell transplantation holds promise for promoting anatomical repair and functional recovery after traumatic or ischemic injuries to the CNS. Harnessing stem cells with therapeutic genes of interest is regarded as an attractive approach to augment therapeutic benefits of stem cell grafts.
The advantage of stem-cell-mediated gene transfer is the engraftibility of stem cells that can ensure a long-term and stable expression of therapeutic genes. In addition, stem-cell-gene interaction may synergistically amplify therapeutic benefits. Delivery of classical neurotrophic factor genes provided neuroprotective and pro-regenerative effects in various injury models. Some studies employed therapeutic genes targeting post-injury microenvironment to support endogenous repair. Recent trials of stem-cell-mediated transfer of nonclassical growth factors showed relatively novel biological effects. Combinatorial strategies seem to have the potential to improve therapeutic efficacy.
Future development of induced pluripotent stem cells and novel scaffolding biomaterials will greatly expedite the advances in ex vivo gene therapy to treat CNS injury. Before moving to a clinical stage, rigorous preclinical evaluations are needed to identify an optimal gene or gene combination in different injury settings. Improving the safety of viral vectors will be a critical prerequisite for the clinical translation.
干细胞移植有望促进中枢神经系统创伤或缺血性损伤后的解剖修复和功能恢复。利用具有治疗相关基因的干细胞被认为是增强干细胞移植物治疗效果的一种有吸引力的方法。
与干细胞相关的基因转移的优势在于可植入的干细胞能够确保治疗相关基因的长期稳定表达。此外，干细胞与基因的相互作用可能会协同放大治疗效果。在各种损伤模型中，经典神经营养因子基因的传递提供了神经保护和促进再生的作用。一些研究采用了针对损伤后微环境的治疗基因来支持内源性修复。最近关于干细胞介导的非经典生长因子转移的试验显示出了相对新颖的生物学效应。组合策略似乎有可能提高治疗效果。
诱导多能干细胞和新型支架生物材料的未来发展将极大地促进治疗中枢神经系统损伤的体外基因治疗的进展。在进入临床阶段之前，需要进行严格的临床前评估，以确定不同损伤环境下的最佳基因或基因组合。提高病毒载体的安全性是临床转化的关键前提。
