Abstract

Background: We explored the effects of INF-γ-modified Bone Marrow Mesenchymal Stem Cells (BMSCs) on the distribution and inhibition of tumour tissues.

Methodology: BALB/c mouse BMSCs were cultured, isolated and identified by flow cytometry. Constructed a lent viral expression vector for the INF-γ gene; BMSCs transfected in vitro were labelled with SYBR Green I fluorescent dye and detected by fluorescent quantitative Polymerase Chain Reaction (qPCR). A blank BALB/c nude mouse control group was randomly selected and the remaining mice were inoculated with glioma cells in the armpit for modelling and the nude mice were randomly divided into model, BMSC and INF-γ+BMSC groups. After 14 days of treatment, during which the long and short diameters of tumours were measured every other day, calculated the tumour volume in tumour-bearing nude mice for each group. Then, observed the distribution of fluorescent BMSCs in nude mice transfected with INF-γ through laser confocal microscopy. Tumour tissues of nude mice were subjected to Terminal Deoxynucleotidyl Transferase dUTP Nick-End Labelling (TUNEL) staining and the number of positive cells was determined.

Results: BMSCs were cultured in-vivo and exhibited adherent growth. Flow cytometry indicated that CD44 (98.01%) and CD105 (96.17%) were overexpressed, whereas the CD34 (1.46%), CD45 (1.32%) and CD11b (1.48%) expression levels were low, indicating that the latter were BMSCs. Fluorescence analysis and PCR were applied to confirm INF-γ transfection into the BMSCs. Immunofluorescence staining showed clear accumulation of BMSCs in nude mouse tissues, with no fluorescence observed in the model group. TUNEL staining showed a higher apoptosis rate in the INF-γ+BMSC group than in the model group (P<0.05). On day 9, the tumour volume differed significantly between the INF-γ+BMSC group and the other groups (P<0.05).

Conclusion: A lentiviral vector effectively transfected the INF-γ gene into BMSCs, where it was homed and distributed to tumour tissues, significantly inhibiting tumour growth.

Keywords: Bone marrow mesenchymal stem cells; Gene modification; Glioma; Interferon gamma (INF-γ); Tumour-bearing nude mice