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Experimental study on the effect of BMSCs premodified with connexin 43 transfection as a mediator of HSV-tk suicide gene directed against invasive glioma cells in vivo

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Author:
No author available
Journal Title:
CHINESE JOURNAL OF NEUROSURGERY
Issue:
4
DOI:
10.3760/cma.j.issn.1001-2346.2009.04.033
Key Word:
骨髓间充质干细胞;神经胶质瘤;CX43;基因治疗;BMSCs;Glioma;CX43;Gene therapy

Abstract: objective To study the therapeutic effect of bone marrow mesenehymal stem cells (BMSCs)as mediator of HSV-tk suicide gene directed against invagive glioma cells,which were premodified with connexin 43 transfection for enhancing the bystander effect.Methods CX43 plagmid wastransfected into C6 glioma cells by liposorne,and HSV-tk Was transfected into BMSCs mediated by adenovirus.The SD rats were divided into four groups:(1)C6 group:C6 glioma cells were injected into right caudate nucleus stereotsctically;(2)CX43-C6 group:instead of C6 cells,C6 cells transfected with CX43(CX43-C6)were injected;(3)tk-BMSCs/C6/GCV and(4)tk-BMSCs/CX43-C6/GCV group:five days after 05 or CX43-C6 cells implantation.tk-BMSCs were iniected stereotaetically with the same coordination,and GCV Wag given intraperitoneally 3 days later in consecutive 14 days.The general status and dynamic MRl were examined regularly.The survival rate of the rats was observed.Tumor specimens were removed to detect cell proliferation activity and apeptosis of both central and borderline regions in glionms.Results All the rats in C6 group died within 20 days,and the mean survival time of CX43-C6 group was 42 days.However.the mean survival time of rats in tk-BMSCs/G6/GCV group and tk-BMSCs/CX43-C6/GCVgroup was prolonged,and some of the tumors were disappeared completely.The expression of PCNA was decreased while the apoptotic cells were increased in the C6 and CX43-C6 gliomas treated with tk-BMSCs/GCV system.Conclusion The tk-BMSCs/GCV system is all effective approach for the treatment of invagive gliomas and its therapeutic effect may be enhanced by co-transfection of CX43 into glioma cells.

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