title: Systemic anticancer neural stem cells in combination with a cardiac glycoside for glioblastoma therapy.
abstract: The tumor-tropic properties of neural stem cells (NSCs) have been shown to serve as a novel strategy to deliver therapeutic genes to tumors. Recently, we have reported that the cardiac glycoside lanatoside C (Lan C) sensitizes glioma cells to the anticancer agent tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Here, we engineered an FDA-approved human NSC line to synthesize and secrete TRAIL and the Gaussia luciferase (Gluc) blood reporter. We showed that upon systemic injection, these cells selectively migrate toward tumors in the mice brain across the blood-brain barrier, target invasive glioma stem-like cells, and induce tumor regression when combined with Lan C. Gluc blood assay revealed that 30% of NSCs survived 1 day postsystemic injection and around 0.5% of these cells remained viable after 5 weeks in glioma-bearing mice. This study demonstrates the potential of systemic injection of NSCs to deliver anticancer agents, such as TRAIL, which yields glioma regression when combined with Lan C.
authors.affiliation: Experimental Therapeutics and Molecular Imaging Laboratory, Neuroscience Center, Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA; Program in Neuroscience, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Teng
authors.forename: Seyedali
authors.initials: S
authors.lastname: Hejazi
authors.forename: Christian E
authors.initials: CE
authors.lastname: Badr
authors.forename: Bakhos A
authors.initials: BA
authors.lastname: Tannous
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001932:Brain Neoplasms / Q000473:pathology*; D002301:Cardiac Glycosides / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D018920:Coculture Techniques; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D015316:Genetic Therapy / Q000379:methods*; D005909:Glioblastoma / Q000473:pathology*; D006801:Humans; D007799:Lanatosides / Q000494:pharmacology; D051379:Mice; D008819:Mice, Nude; D058953:Neural Stem Cells / Q000637:transplantation*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000008:administration & dosage* / Q000235:genetics; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
chemical_list: D002301:Cardiac Glycosides; D007799:Lanatosides; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; C018548:lanatoside C
keywords: Cardiac glycoside; Glioblastoma; Neural stem cells; Tumor necrosis factor-related apoptosis-inducing ligand; Tumor-tropic