[Effect of bone marrow stromal cells transfected with interleukin 18 on growth of intracranial glioma in rats].
OBJECTIVE
Because of the invasion and immune escape characteristics, surgical resection, radiotherapy, and chemotherapy had no definite curative effects on intracranial glioma. Because bone marrow stromal cells (BMSCs) can track migrating cells, and interleukin 18 (IL-18) can enhance antitumor immune reaction, this study was to explore the effect of IL-18-transfected BMSCs on growth of glioma in rats.


METHODS
Pure BMSCs were obtained by culturing rat bone marrow cells and identified by flow cytometry (FCM). BMSCs were transfected with retrovirus LXSN/IL-18 to prepare BMSCs/IL-18. IL-18 genetic transcription and expression were assessed by reverse transcription-polymerase chain reaction (RT-PCR) and immunofluorescence. The characteristic variations of BMSCs were detected by MTT assay, FCM, and immunofluorescence. The effect of BMSCs/IL-18 on activation of T cells was evaluated by ELISA. Glioma-bearing rats were divided into BMSCs group, BMSCs/IL-18 group, PBS group, and control group and received relevant treatments. The effect of BMSCs/IL-18 on growth of glioma was observed.


RESULTS
IL-18 gene was expressed stably in BMSCs/IL-18. The proliferation speed of BMSCs/IL-18 was slower than that of BMSCs. The secretion of interferon-gamma (IFN-gamma) from rat spleen lymphocytes in BMSCs/IL-18 group was 9 times more than that in BMSCs group. Tumor volume was (18.26+/-6.84) mm(3) in BMSCs group, (6.37+/-1.52) mm(3) in BMSCs/IL-18 group, (22.48+/-6.02) mm(3) in PBS group, and (21.06+/-5.83) mm(3) in control group; survival time of the rats was (25.3+/-6.4) days, (84.7+/-16.3) days, (21.6+/-4.7) days, and (22.5+/-6.2) days, respectively. After transplantation of BMSCs/IL-18, CD4(+) T cells in glioma were increased to 37.7+/-3.5 and CD8(+) T cells were increased to 32.3+/-4.5 in each field of view (x200).


CONCLUSIONS
BMSCs/IL-18 could express IL-18 gene stably, and have definite therapeutic effect on glioma in rats.
Li
Chun-Hui
CH
Department of Neurosurgery, The Second Affiliated Hospital, Hebei Medical University, Shijiazhuang, Hebei, 050000, P. R. China.
Jiao
Bao-Hua
BH
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D001932:Brain Neoplasms / Q000473:pathology / Q000628:therapy*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D049109:Cell Proliferation; D002478:Cells, Cultured; D015316:Genetic Therapy / Q000379:methods; D005910:Glioma / Q000473:pathology / Q000628:therapy*; D007371:Interferon-gamma / Q000378:metabolism; D020382:Interleukin-18 / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D009368:Neoplasm Transplantation; D010957:Plasmids; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012190:Retroviridae / Q000235:genetics; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism* / Q000637:transplantation; D014162:Transfection
D020382:Interleukin-18; D007371:Interferon-gamma