Most importantly, the complex cross-talk between a variety of signaling pathways associated with GSCs support our findings that ‘PDGF/IL6/E&F’, ‘PDGF/PlGF/E&F’ and ‘PEDF/SHH/E&F’ could be alternative supplements to standard E&F alone, by their synergistic promoting effects on the establishment of GSCs from IDH1-mut glioblastomas and LGGs. Here, SHH is linked to glioblastoma.