Research Article

Monitoring the Bystander Killing Effect of Human Multipotent Stem Cells for Treatment of Malignant Brain Tumors

Figure 6

Follow-up of suicide gene therapy using hMultistem as cellular vehicles in the Hs683 oligodendroglioma model by using multimodal in vivo imaging and histology. (a) MR images of a representative animal from the sham, PBS, and GCV treated groups show a comparable tumor growth prior to hMultistem injection on T2-weighted MR images (upper row for each group). While there is little hypointense contrast visible on 3D -weighted MR images (lower row for each group), the distribution of SPIO labeled hMultistem cells could clearly be detected due to their hypointense contrast in the PBS and GCV treated group. When tumors grew larger, the hypointense voxels got more dispersed over time. (b) BLI of representative animals. The fLuc expression of the stem cells was clearly detectable after engraftment and only diminished after 14 days. (c) One week after the end of therapy, animals developed symptoms after which histological analysis was performed. Masson’s trichrome staining (upper left) of all animals showed very large tumors. Prussian blue (upper right) staining was also performed which confirmed the presence of iron in PBS and GCV treated animals. Finally, Iba1 staining (bottom) was performed which showed a predominant absence of activated microglia in all treatment groups. Some minor microglial activation was however detectable around the tumor.