拓扑异构酶II-alpha在脊髓损伤后活化星形胶质细胞干细胞特性获得和维持中的作用及机制研究

Spinal cord injury (SCI) is the difficulty and focus in the field of nerve injury and repair,so far,there is no substantive treatment. Stem cell therapy is considered to be an important direction of development, especially the endogenous stem cell research and use. Glial cell activation(gliosis)after spinal cord injury in the local microenvironment, especially astrocytes activation (astrogliosis) is an important biological phenomenon. One subset of activated astrocytes has been confirmed to have the characteristics of the neural stem cells or precursor cells, but there is very little research on the properties of these cells. In order to find the important molecules involved in the initializing and maintaining the stem cell properties of reactive astrocytes in the injuried spinal cord, with sorting GFP-positive cells from normal and injury GFAP-GFP mice around the spinal cord and gene chip screening,we discovered and confirmed that the topoisomerase II-alpha is specifically expressed in Gfap and Nestin positive cells localized in the injuried spinal cord. In this study, we integrated use of technical means of cell biology, molecular biology, and morphology, and further in-depth research topoisomerase II-alpha in activated astrocytes in self-renewal and pluripotency of stem cell properties, to provide important theoretical basis of endogenous stem cell treatment strategy for spinal cord injury.

脊髓损伤是神经损伤修复领域中的难点和重点，目前还没有有效的治疗手段。干细胞治疗被认为是一个重要的发展方向，尤其是内源性干细胞的研究和运用。脊髓损伤后的局部微环境中胶质细胞活化，尤其是星形胶质细胞的活化是一个重要的生物学现象。活化的星形胶质细胞中有一类亚群被证实具有某些神经干细胞或前体细胞的特性，但目前对这类细胞特性的相关研究甚少。为了寻找参与起始和维持脊髓损伤后活化星形胶质干细胞特性的重要分子，我们分选正常和损伤GFAP-GFP小鼠脊髓组织GFP标记的细胞，通过基因芯片的差异比对筛选，发现拓扑异构酶II-alpha特异表达在脊髓损伤后Gfap、Nestin阳性的细胞中。本研究将综合运用细胞生物学、分子生物学和形态学等技术手段，进一步深入研究拓扑异构酶II-alpha在干细胞样活化星形胶质细胞中自我更新和多能性维持的作用，以期为应用内源性干细胞治疗脊髓损伤提供新的思路和理论依据。

脊髓损伤是神经损伤修复领域中的难点和重点，目前还没有有效的治疗手段。干细胞治疗被认为是一个重要的发展方向，尤其是内源性干细胞的研究和运用。脊髓损伤后的局部微环境中胶质细胞活化，尤其是星形胶质细胞的活化是一个重要的生物学现象。活化的星形胶质细胞中有一类亚群被证实具有某些神经干细胞或前体细胞的特性，但目前对这类细胞特性的相关研究甚少。为了寻找参与起始和维持脊髓损伤后活化星形胶质干细胞特性的重要分子，我们分选正常和损伤GFAP-GFP小鼠脊髓组织GFP标记的细胞，通过基因芯片的差异比对筛选，发现拓扑异构酶II-alpha特异表达在脊髓损伤后Gfap、Nestin阳性的细胞中。本研究综合运用细胞生物学、分子生物学和形态学等技术手段，进一步深入研究拓扑异构酶II-alpha在干细胞样活化星形胶质细胞中自我更新和多能性维持的作用，以期为应用内源性干细胞治疗脊髓损伤提供新的思路和理论依据。我们首次系统检测了TopoIIa在正常中枢神经系统发育与脊髓损伤后活化胶质细胞上的表达；首次在体外证实了TopoIIa对活化星形胶质细胞来源干细胞自我更新能力的影响。我们自行构建了TopoIIa的flox条件敲除小鼠，下一步我们将按照既定计划，在体水平探索TopoIIa对中枢系统损伤后活化胶质细胞来源干细胞命运的影响。