title: Therapeutically engineered induced neural stem cells are tumour-homing and inhibit progression of glioblastoma.
abstract: Transdifferentiation (TD) is a recent advancement in somatic cell reprogramming. The direct conversion of TD eliminates the pluripotent intermediate state to create cells that are ideal for personalized cell therapy. Here we provide evidence that TD-derived induced neural stem cells (iNSCs) are an efficacious therapeutic strategy for brain cancer. We find that iNSCs genetically engineered with optical reporters and tumouricidal gene products retain the capacity to differentiate and induced apoptosis in co-cultured human glioblastoma cells. Time-lapse imaging shows that iNSCs are tumouritropic, homing rapidly to co-cultured glioblastoma cells and migrating extensively to distant tumour foci in the murine brain. Multimodality imaging reveals that iNSC delivery of the anticancer molecule TRAIL decreases the growth of established solid and diffuse patient-derived orthotopic glioblastoma xenografts 230- and 20-fold, respectively, while significantly prolonging the median mouse survival. These findings establish a strategy for creating autologous cell-based therapies to treat patients with aggressive forms of brain cancer.
authors.affiliation: Division of Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
authors.forename: Juli R
authors.initials: JR
authors.lastname: Bagó
authors.affiliation: Division of Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
authors.forename: Adolfo
authors.initials: A
authors.lastname: Alfonso-Pecchio
authors.affiliation: Division of Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
authors.forename: Onyi
authors.initials: O
authors.lastname: Okolie
authors.affiliation: Department of Genetics, UNC Human Pluripotent Stem Cell Core, UNC School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.|Neuroscience Center, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
authors.forename: Raluca
authors.initials: R
authors.lastname: Dumitru
authors.affiliation: Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.|Division of Neuropathology, Department of Pathology and Laboratory Medicine, UNC School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Rinkenbaugh
authors.affiliation: Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
authors.forename: Albert S
authors.initials: AS
authors.lastname: Baldwin
authors.affiliation: Neuroscience Center, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.|Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.|Division of Neuropathology, Department of Pathology and Laboratory Medicine, UNC School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.|Department of Neurology, UNC School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
authors.forename: C Ryan
authors.initials: CR
authors.lastname: Miller
authors.affiliation: Department of Cell Biology and Physiology, UNC School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
authors.forename: Scott T
authors.initials: ST
authors.lastname: Magness
authors.affiliation: Division of Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.|Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.|Biomedical Research Imaging Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
authors.forename: Shawn D
authors.initials: SD
authors.lastname: Hingtgen
mesh_terms: D000818:Animals; D001253:Astrocytes; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D005347:Fibroblasts; D005909:Glioblastoma; D006801:Humans; D057026:Induced Pluripotent Stem Cells; D051379:Mice; D009374:Neoplasms, Experimental; D058953:Neural Stem Cells / Q000166:cytology* / Q000502:physiology*
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