Figure 4. sECM-encapsulated mNSC-S-TRAIL cells transplanted into the tumor resection cavity increase survival of mice.

(a) Light photomicrograph of the resection cavity containing sECM-encapsulated mNSCs (outlined area). (b–d) mNSC-GFP-Fluc cells encapsulated in sECM were implanted intracranially in the resection cavity, and the mice were injected with Angiosense-750 (blue) intravenously and imaged by IVM and by serial Fluc bioluminescence imaging. (b) Fluorescence photomicrograph showing mNSCs (green) targeting residual GBM cells (red) in a tumor resection cavity with leaky vasculature (blue). (c) Hematoxylin and eosin image of sECM-encapsulated mNSC-GFP-Fluc cells implanted (outlined area) in the resection cavity. (d) Higher magnification fluorescence photomicrograph showing mNSCs (green) targeting residual GBM cells (red) indicated by arrows in a tumor resection cavity with leaky vasculature (blue). (e) Plot and representative images from day 7 (dashed outlines) of the relative mean Fluc signal intensity of mNSC-GFP-Fluc cells in suspension or encapsulated in sECM, placed in the GBM resection cavity (*P < 0.05 versus encapsulated mNSCs). (f,g) mNSC-S-TRAIL or mNSC-GFP-Rluc cells encapsulated in sECM or mNSC-S-TRAIL cells in suspension were implanted intracranially in the tumor resection cavity. (f) TRAIL-mediated caspase-3/7 activation and tumor volumes as assessed by serial bioluminescence imaging after aminoluciferin and luciferin injections, respectively. Caspase-3/7 activity, *P < 0.05 versus mNSC-S-TRAIL; tumor volumes, *P < 0.05 versus controls. (g) Kaplan-Meier survival curves. P < 0.05, resected + GFP-Rluc cells in sECM versus un-resected; P < 0.05, resected + mNSC-S-TRAIL cells in sECM versus resected + mNSC-S-TRAIL cells in suspension. Scale bars, 200 µm (b) and 100 µm (c,d). Original magnification, ×4 (a). Data are mean ± s.e.m.