少突胶质前体细胞延长神经胶质母细胞瘤大鼠高剂量放疗后的生存期

背景：胶质母细胞瘤是成人常见的恶性脑肿瘤，目前尚缺乏有效的治疗方法，临床预后不良。目的：观察单次高剂量放疗对神经胶质母细胞瘤的疗效，以及少突胶质前体细胞修复放射性脑损伤的可行性。方法：通过质粒转染构建可表达荧光素酶(Luc)的人源性U-87 MG肿瘤细胞系。15只Fisher 344大鼠制备Luc-U-87 MG神经胶质母细胞瘤模型，随机分为肿瘤模型组(n=3)、放疗组(n=6)和放疗+细胞移植组(n=6)，后两组放疗方式为单次80 Gy辐射；放疗后5周，放疗+细胞移植组大鼠联合少突胶质前体细胞移植治疗。利用活体成像的方法监测肿瘤细胞的生长；MRI观察放疗引起的脑组织影像学变化；采用KaplanMeier生存分析明确细胞移植对放疗大鼠生存率的影响；对移植细胞的存活及分化情况进行组织学观察。结果与结论：(1)体外生物成像示转染后的U-87 MG细胞与Luc底物产生反应发出生物信号，信号强度与转染细胞的数量呈线性正相关；(2)动物活体成像结果显示，肿瘤模型大鼠的颅内胶质母细胞瘤信号持续上升直至接种第5周(全部死亡)；放疗大鼠在治疗后2周，肿瘤信号开始衰减，4周后未见肿瘤发光信号；(3)放疗...

Oligodendrocyte progenitor cells prolong the survival of glioblastoma-bearing rats after high-dose radiotherapy

BACKGROUND: Glioblastoma is a common malignant brain tumor for adults with poor prognosis and remains lack of efficient treatments. OBJECTIVE: To investigate the efficacy of single high-dose radiotherapy on glioblastoma and the feasibility of oligodendrocyte progenitor cells in the repair of radiation-induced brain injury. METHODS: Plasmid transfection was used to develop human U-87 MG cell line expressing luciferase (Luc). Fifteen Fisher 344 rats bearing Luc-U-87 MG glioblastoma were randomly divided into tumor model group (n=3), radiotherapy group (n=6), and oligodendrocyte progenitor cell transplantation group (n=6). Single high-dose radiotherapy (80 Gy) was given in the latter two groups and cell transplantation was performed in the last group 5 weeks after radiotherapy. In vivo imaging was employed to monitor the tumor growth. MRI was performed to observe the cerebral structure changes induced by radiation. Kaplan-Meier analysis was used to determine the effect of cell transplantation on the survival rate of irradiated rats. Survival and differentiation of transplanted cells were histologically observed. RESULTS AND CONCLUSION: In vitro imaging results showed that the transfected U-87 MG cells reacted with the Luc substrate to produce bioluminescence signals. Signal intensity had a positive linear correlation with the number of transfected cells. Intracranial glioblastoma signals in the tumor model rats continued to increase until their death at 5 weeks after tumor inoculation. Two weeks after radiotherapy, the bioluminescence signal started to decline in the radiotherapy group and was not detected at 4 weeks. Necrotic tumor tissue was observed on T2WI at 5 weeks after radiotherapy but not at 10 weeks, at which timepoint the abnormal signal indicative of brain injury appeared. However, there were no similar signals in the cell transplantation group. Fifteen weeks later, T2WI showed hypo-and hyperintensity signals in the brain parenchyma for all the rats which received irradiation, whereas the injury signal in the radiotherapy group was stronger than that in the cell transplantation group. The survival analysis results revealed the median survival time of the tumor model group, radiotherapy group, and cell transplantation group were 30, 114.5, and 232.5 days, respectively. There were significant differences in the median survival time among groups (P < 0.01). Histological findings showed the transplanted cells survived with multipolarity and some of them expressed myelin basic protein. Moreover, the expression of myelin basic protein in the cell transplantation group was significantly higher than that in the radiotherapy group (P < 0.01). All these findings indicate that single high-dose radiotherapy can effective treat human-derived glioblastoma in rats. Oligodendrocyte progenitor cells transplanted are capable of repairing radiation-induced brain injury, thereby prolonging the survival of irradiated rats. Remyelination is one of the mechanisms accounting for brain tissue repair. © 2023, Publishing House of Chinese Journal of Tissue Engineering Research. All rights reserved.