van der Maazen R W, Verhagen I, Kleiboer B J, van der Kogel A J
Institute of Radiotherapy, University of Nijmegen, The Netherlands.
Radiother Oncol. 1991 Apr;20(4):258-64. doi: 10.1016/0167-8140(91)90125-z.
The cellular basis of radiation-induced demyelination and white matter necrosis of the central nervous system (CNS), is poorly understood. Glial cells responsible for myelination in the CNS might be the target cells of this type of damage. Glial cells with stem cell properties derived from the perinatal and adult rat CNS can be cultured in vitro. These cells are able to differentiate into oligodendrocytes or type-2 astrocytes (O-2A) depending on the culture conditions. Growth factors produced by monolayers of type-1 astrocytes inhibit premature differentiation of O-2A progenitor cells and allow colony formation. A method which employs these monolayers of type-1 astrocytes to culture O-2A progenitor cells has been adapted to allow the analysis of colonies of surviving cells after X-irradiation. In vitro survival curves were obtained for glial progenitor cells derived from perinatal and adult optic nerves. The intrinsic radiosensitivity of perinatal and adult O-2A progenitor cells showed a large difference. Perinatal O-2A progenitor cells are quite radiosensitive, in contrast to adult O-2A progenitor cells. For both cell types an inverse relationship was found between the dose and the size of colonies derived from surviving cells. Surviving O-2A progenitor cells maintain their ability to differentiate into oligodendrocytes or type-2 astrocytes. This system to assess radiation-induced damage to glial progenitor cells in vitro seems to have a great potential in unraveling the cellular basis of radiation-induced demyelinating syndromes of the CNS.
中枢神经系统（CNS）辐射诱导的脱髓鞘和白质坏死的细胞基础，目前了解甚少。中枢神经系统中负责髓鞘形成的神经胶质细胞可能是这类损伤的靶细胞。源自围产期和成年大鼠中枢神经系统的具有干细胞特性的神经胶质细胞可在体外培养。这些细胞能够根据培养条件分化为少突胶质细胞或2型星形胶质细胞（O-2A）。1型星形胶质细胞单层产生的生长因子可抑制O-2A祖细胞的过早分化并促进集落形成。一种利用这些1型星形胶质细胞单层培养O-2A祖细胞的方法已被改进，以分析X射线照射后存活细胞的集落。获得了源自围产期和成年视神经的神经胶质祖细胞的体外存活曲线。围产期和成年O-2A祖细胞的内在放射敏感性存在很大差异。与成年O-2A祖细胞相比，围产期O-2A祖细胞对辐射相当敏感。对于这两种细胞类型，均发现剂量与存活细胞衍生的集落大小之间呈反比关系。存活的O-2A祖细胞保持其分化为少突胶质细胞或2型星形胶质细胞的能力。这种体外评估辐射对神经胶质祖细胞损伤的系统，在揭示中枢神经系统辐射诱导的脱髓鞘综合征的细胞基础方面似乎具有很大潜力。
