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기초 : 자살유전자를 이입한 사람 신경줄기세포를 이용한 악성 신경교종의 유전자 치료
안영민 ( Young Min Ahn ),조경기 ( Kyung Gi Cho ),이창미 ( Chang Mi Lee ),방종희 ( Joung Hee Bang ),류명이 ( Myung Yi Ryu ),김세중 ( Se Joong Kim ),서혜영 ( Hae Young Suh ),김승업 ( Seung Eop Kim ) 대한뇌종양학회 2006 대한뇌종양학회지 Vol.5 No.2
Introduction : Despite the advanced neurosurgical techniques and various multimodal therapeutic approach have been developed for malignant gliomas, these can not save the patients from the tumors due to infiltrating behavior of glioma cells. Here the authors investigated the possibility of treatment for the malignant gliomas with neural stem cell(HB1.F3) transduced with suicidal gene using the tropism of stem cells. Materials and Methods : E.coli cytosine deaminase(CD) is an enzyme that catalyzes the conversion of noncytotoxic 5- FC to the cytotoxic and radiosensitizing drug 5-FU. Cytotoxic 5-FU and its toxic metabolites can readily diffuse into surrounding tumor cells giving CD. HB1.F3 were transduced with retroviral vectors expressing the E.coli CD. Rats were implanted with U373MG, U251MG human glioblastoma(hGM) cell line and F3/CD were injected directly into the tumor mass 6 days later. The rats with tumors were injected IP 5-FC or saline daily for 7 days since 6 days after implantation of tumors. Results : HB1.F3 which were injected into the contralateral hemisphere to the tumor implantation site migrated through the corpus callosum to the tumor cells 3 days after hGM transplantation . The growth inhibition of 5-FU treated cells in comparison to untreated controls was remarkable in vitro. The tumor mass in the rats with transplantation of F3/CD were reduced markedly in size comparing to that with F3 after injection of 5-FC . Conclusions : The human neural stem cells can trace to the glioma cells in the rat brain. 5-FC systemic treatment with direct transplantation of F3/CD reduces tumor size. Our data indicates that suicide gene therapy using neural stem cells would be promising as a new therapeutic approach for malignant glioma.
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