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Gene transfer mediated by stem cell grafts to treat CNS injury.

机译:干细胞移植介导的基因转移可治疗中枢神经系统损伤。

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INTRODUCTION: 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. AREAS COVERED: 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. EXPERT OPINION: 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.
机译:简介:干细胞移植有望在中枢神经系统受到外伤或缺血性损伤后促进解剖修复和功能恢复。利用感兴趣的治疗基因来治疗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。覆盖的领域:干细胞介导的基因转移的优势是干细胞的可移植性,可以确保治疗性基因的长期稳定表达。另外,干细胞-基因相互作用可以协同增加治疗益处。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再生作用。一些研究采用靶向损伤后微环境的治疗基因来支持内源性修复。干细胞介导的非经典生长因子转移的最新试验显示了相对新颖的生物学效应。组合策略似乎具有改善治疗功效的潜力。专家意见:诱导型多能干细胞和新型支架生物材料的未来发展将大大加快离体基因疗法治疗中枢神经系统损伤的进展。在进入临床阶段之前,需要进行严格的临床前评估,以鉴定出不同损伤情况下的最佳基因或基因组合。改善病毒载体的安全性将是临床翻译的关键前提。

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