Cytotoxic human pediatric stem cells derived from patient skin suppress and delay regrowth of post-surgical medulloblastoma.

<p>Illustration of the reprogramming scheme which converts human pediatric fibroblasts into cytotoxic human pediatric induced neural stem cells (hp-iNSC^tk, A). hp-iNSC express the thymidine kinase/RFP lentiviral vector as determined by white light (B) and fluorescent (C) images. Schematic depiction of hp-iNSC^tk migration assay in the presence (+D283) or absence (control) of MB cells (D). The cells were seeded 500 μm apart from each other and migration was tracked over the course of 24h by fluorescent and white light imaging (E). Summary graph shows hp-iNSC^tk cells migrate further in the presence D283-GFPFL cells than in the absence of these cells (3.3-fold, P < 0001, F). D283-GFPFL cells were seeded with varying concentrations of hp-iNSC^tk and tumor cell viability was measured by luminescence 24h after GCV administration (G). Representative BLI images (H) and summary graph (I) showing the <i>in vivo</i> therapeutic efficacy of cytotoxic NSC therapy (hp-iNSC^tk/GCV) compared to control (hp-iNSC^tk). hp-iNSC^tk/GCV treatment extended survival of mice compared to the control hp-iNSC^tk (53 vs 43 days) (J). Post-mortem histopathological analysis showed the presence of larger recurrent tumors in control mice (K) compared with treatment (L) groups. RC and T denotes resection cavity and tumor, respectively. Original magnification: 100X (B, C, E, K, L). Scale bars = 100 μm. n = 5–6 in each group.