Fig. 2. Depletion of pericytes in pericyte^high GBMs improves the therapeutic efficacy of TMZ.

a Schematic diagram of Desmin promoter-driven expression of HsvTK vector and control vector. Gene therapy was achieved through administration of GCV, which is converted to a toxic metabolite to eliminate cells expressing HsvTK. b Schematic diagram of the combined treatment of TMZ and GCV in mice bearing GBM-2 (pericyte^high) xenografts expressing DesPro-TK or control DesPro. GCV (50 mg/kg, i.p.) was given for 4 days with 1-day interval since Day 15 and TMZ (5 mg/kg, i.p.) was given for 3 consecutive days since Day 16 after tumor implantation. Xenograft growth was monitored by bioluminescence imaging on Day 15 and Day 23 after tumor implantation. IVIS, In Vivo Imaging System. c, d In vivo bioluminescence images (c) and quantification (d) of tumor growth of human GBM-2 xenografts treated with GCV together with or without TMZ on Day 15 and Day 23 after tumor implantation. ns, not significant. *P < 0.05. n = 5 for each group. e Kaplan–Meier survival analysis of mice bearing GBM-2 xenografts with the indicated treatment. n = 5 for each group. f, g Immunofluorescence staining (f) and quantification (g) of pericyte marker α-SMA (green) in GBM-2 xenografts treated with GCV together with or without TMZ. ns, not significant. *P < 0.05. Scale bars, 25 μm. h, i Immunofluorescence staining (h) and quantification (i) of γ-H2AX (red)-positive cells in GBM-2 xenografts treated with GCV together with or without TMZ. **P < 0.01. Scale bars, 25 μm. j TMZ concentration in GBM-2 xenografts and blood in mice expressing DesPro-TK or control DesPro with GCV treatment. n = 4 for each group.