[Anti-glioma activity of treatment by bone marrow stromal cells transfected with HSV-tk in the rat].
OBJECTIVE
To study the anti-glioma activity of treatment by bone marrow stromal cells (BMSCs) transfected with AdCMV-tk containing HSV-tk gene in rats.


METHODS
Primary cultured BMSCs were obtained and transfected with HSV-tk (BMSCs/tk) and were injected into contralateral brain of glioma-bearing rats to observe their tropism for glioma cells. RT-PCR was performed to examine the transduct of tk gene after it was transduced into BMSCs. C6 glioma cells were co-cultured with BMSCs transfected with HSV-tk. MTT test was performed to examine its antitumor activity. BMSCs, after being transfected with HSV-tk, were injected into contralateral brain tissue of glioma-bearing rats to show their in vivo antitumor activity. Dynamic MRI was performed to monitor the development of intracranial glioma.


RESULTS
Purified BMSCs were obtained by primary cultured bone marrow cells. After being transfected with HSV-TK, the cells still stably displayed extensive tropism for intracranial glioma and transcripted tk gene. RT-PCR showed that BMSCs/tk were transduced tk gene obviously at 21 days after AdCMV-tk transfection. BMSCs/tk showed a clear bystander effect after being co-cultured with C6 glioma cells in vitro. TUNEL assay showed that BMSCs/tk could obviously show bystander effect and induce apoptosis of glioma cells in vivo with an apoptosis positive ratio of 20.38% +/- 2.57%, showing a statistically significant difference in comparison with BMSCs group (2.56% +/- 0.52%, P = 0.023) and control group (2.74% +/- 0.38%, P = 0.025). Compared with the control group (21.40 +/- 1.63 days), BMSCs/tk transplantation significantly prolonged the survival time of glioma-bearing rats (52.60 +/- 13.11 days, P = 0.000). MRI detection showed that the least volume of intracranial glioma in BMSCs/tk group (8.28 +/- 2.64 mm3), significantly smaller than that in BMSCs group (134.51 +/- 16.37 mm3, P = 0.001) and control group (147.22 +/- 31.05 mm3, P = 0.001). Some of the intracranial gliomaa disappeared after transplantation of BMSCs/tk.


CONCLUSIONS
BMSCs transfected with AdCMV-tk may become an effective therapy method in the treatment for glioma.
Li
Chun-hui
CH
Department of Neurosurgery, the Second Affiliated Hospital of Hebei Medical University, Shijiazhuang 050000, China.
Jiao
Bao-hua
BH
D000818:Animals; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000166:cytology; D001921:Brain / Q000473:pathology; D024201:Bystander Effect; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D015316:Genetic Therapy / Q000379:methods; D005910:Glioma / Q000473:pathology / Q000628:therapy*; D008279:Magnetic Resonance Imaging; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018139:Simplexvirus / Q000201:enzymology*; D017154:Stromal Cells / Q000166:cytology / Q000201:enzymology* / Q000637:transplantation; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D013937:Thymidine Kinase