Greenberger J S
Department of Radiation Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213-2532, USA.
Gene Ther. 2008 Jan;15(2):100-8. doi: 10.1038/sj.gt.3303004. Epub 2007 Aug 16.
Cytotoxic exposure of bone marrow and other non-hematopoietic organs containing self-renewing stem cell populations is associated with damage to the supportive microenvironment. Recent evidence indicates that radical oxygen species resulting from the initial oxidative stress persist for months after ionizing irradiation exposure of tissues including oral cavity, esophagus, lung and bone marrow. Antioxidant gene therapy using manganese superoxide dismutase plasmid liposomes has provided organ-specific radiation protection associated with delay or prevention of acute and late toxicity. Recent evidence has suggested that manganese superoxide dismutase transgene expression in cells of the organ microenvironment contributes significantly to the mechanism of protection. Incorporating this knowledge into designs of novel approaches for stem cell protection is addressed in the present review.
骨髓以及其他含有自我更新干细胞群体的非造血器官受到细胞毒性暴露，与支持性微环境的损伤有关。最近的证据表明，电离辐射暴露于包括口腔、食管、肺和骨髓在内的组织后，由初始氧化应激产生的活性氧会持续存在数月。使用锰超氧化物歧化酶质粒脂质体进行抗氧化基因治疗已提供了器官特异性辐射防护，与延迟或预防急性和晚期毒性相关。最近的证据表明，器官微环境细胞中的锰超氧化物歧化酶转基因表达对保护机制有显著贡献。本综述探讨了将这一知识纳入干细胞保护新方法的设计中。
