Fig 2: Dual inhibition of PDGFR and VEGFR-2 inhibits glioma growth and progression. The primary GBM was induced in Ntv-a;Ink4a-Arf−/−;Pten−/−;LSL-Luc donor mice by RCAS-mediated somatic gene transfer. Single-cell tumor suspension was implanted into recipient mice, followed by treatment. a Schematic approach. b Animal survival was monitored for 70 days after injection (n = 6–7 mice). MS median survival. P values were determined by log-rank tests. c Tumor growth was analyzed by whole-body bioluminescence imaging. Left, representative images. Right, quantitative analysis of integrated luminescence in tumors at day 32–38 (n = 3–6, mean ± SEM). P values were determined by Student’s t test. d Tumor sections were stained with H&E and imaged. Representative data are shown from 3–4 mice/group. Scale bar: 100 μm. e Tumor sections were immunostained with anti-CD31 antibody and imaged. Shown are representative images (n = 3–5 mice). Scale bar: 100 μm

Fig 3: Tumor-associated ECs are resistant to anti-VEGF treatment and have diminished VEGFR-2 expression. a–c ECs were isolated from GBM tumors or peri-tumor tissues of human patients or normal brains. a, b Tumor ECs and normal brain microvascular ECs were treated with a 3 nM Ki8751 or b 10 µg/ml B20 antibody in VEGF-A-containing culture medium, and subjected to cell viability analysis (n = 3, mean ± SEM). c Cell lysates were immunoblotted. d, e The primary GBM in Ntv-a;Ink4a-Arf-/-;Pten-/-;LSL-Luc donor mice was induced by RCAS-mediated somatic gene transfer. Single-cell tumor suspension was injected into Rosa-LSL-tdTomato;Tie2-Cre mice. d Schematic approach. e Single-cell suspension isolated from normal brains or tumors were analyzed by flow cytometry. Left: representative sorting of CD11b- cells. Right: quantitative data (n = 4 mice, mean ± SEM). P value was determined by Student’s t test

Fig 4: Circulating counts of progenitor cells in individuals undergoing CPB at various intra-operative time points in G1 and G2 study individuals.Line graph showing fold change in cell counts for (A) CD34+ (B) HSC (CD34+CD133+) and (C) EPC (CD34+VEGFR2+) in vasoplegic groups namely G1 and G2. Data is plotted as mean ± SEM. *p ≤ 0.05, ** p ≤ 0.01 vs G2 at that point. Mann-Whitney’s test and Wilcoxon matched pair test were employed accordingly.

Fig 5: Fold changes in circulating counts of measured progenitor cells for all 15 on pump cases (4 were considered outlier by statistical package for the social sciences).(A) Line graph showing fold change in single positive cell counts for CD34+, CD133+& VEGFR2+ cells and (B) Line graph summarizing changes in double positive cell counts for HSCs (CD34+CD133+) and EPCs (CD34+VEGFR2+). Data is plotted as mean ± SEM. *p ≤ 0.05, ** p ≤ 0.01 vs post induction, $ p ≤ 0.05, $ $ p ≤ 0.01 vs sternotomy and # vs 6 hours. Mann-Whitney’s test and Wilcoxon matched pair test were employed accordingly.