Fig. 4.

Pharmacodynamics and therapeutic efficacy of MSC-S-TRAIL. (A) MSCs were co-transduced with LV-Gluc-S-TRAIL and LV-GFP-Fluc, and cells and conditioned culture medium were imaged for Fluc and Gluc activity, respectively. Plots show correlation between the different concentrations of cells-Fluc activity and medium-Gluc activity within the ranges tested. (B) MSCs expressing Gluc-S-TRAIL and GFP-Fluc were mixed with Gli36-EGFRvIII glioma cells and implanted s.c. in nude mice. Mice were imaged for Fluc and Gluc activity every week for a period of 2 weeks. (C–H) Serial in vivo bioluminescence imaging of tumor growth following intracranial implantation of Gli36-EGFRvIII-FD glioma cells mixed with MSCs expressing S-TRAIL (MSC-S-TRAIL; D, F, and H) or GFP (MSC-GFP; C, E, and G). One representative mouse image from each group is shown. (I) Relative mean bioluminescent signal intensities after quantification of in vivo images. (J–O) Photomicrographs show presence of cleaved caspase-3 (J) and Ki67-positive cells (M) in brain sections from MSC-S-TRAIL-treated and control mice (K and N) 6 days after implantation. Plot shows the number of cleaved caspase-3 (L) and Ki67 (O) cells in MSC-S-TRAIL and MSC-GFP-treated tumors. (Green, MSCs; red, glioma cells; purple, Ki67 or cleaved caspase-3 expression; original magnification: J, K, M, and N, ×20.)