Intracerebral injections of hMSCs in U87MG orthotopic xenografts. a Schematic drawing of the intracerebral injection of m-Cherry adipose-derived human mesenchymal stem/stromal cells (Ad-hMSCs) (red) and green fluorescent protein (GFP) U87MG cells (green) in cyclosporine immunosuppressed rats. b Microphotographs on fluorescence microscopy of a coronal section of rat brain showing the injection sites at low (left panel; scale bar = 500 μm) and higher (right panel; scale bars = 250 μm) magnification. At 1 week after grafting, the vast majority of the Ad-hMSCs had migrated towards the tumor. c Microphotograph of the tumor epicentre showing Ad-hMSCs that have migrated into the tumor (left panel; scale bar = 40 μm). Detail of a paclitaxel (PTX)-loaded Ad-hMSC lying adjacent to a multinucleated U87MG tumor cell (yellow arrow; scale bar = 25 μm).
d Bar graph showing the percentage of multinucleated U87MG cells in brain xenografts injected with PTX-loaded Ad-hMSCs and in those injected with unloaded Ad-hMSCs (***p < 0.0001). e Kaplan-Meier curves for the survival of rats grafted with U87MG cells (red line), U87MG cells plus Ad-hMSCs (green line), and U87MG cells plus PTX-loaded Ad-hMSCs (blue line). f Bar graph showing the volume of U87MG xenografts in control rats and in rats treated with unloaded Ad-hMSCs and in those treated with PTX-loaded Ad-hMSCs (*p < 0.05). g Bar graph showing cell proliferation, as assessed by Ki67 labeling, in control U87MG xenografts and in those injected with unloaded Ad-hMSCs or with PTX-loaded Ad-hMSCs (***p < 0.0001). h Assessment of microvascular density. Sections of the brain xenograft immunostained with anti-CD34 were acquired, converted into grayscale, and assessed by computerized image analysis. Scale bar = 100 μm. i Bar graph showing microvascular density in control U87MG xenografts and in xenografts injected with unloaded Ad-hMSCs or with PTX-loaded Ad-hMSCs. Values on the y axis represent the percent of the endothelial area (CD34+)/tumor area (EA/tumor area) per microscope field (***p < 0.0001). CNTR control