title: Adipose-derived stem cells as therapeutic delivery vehicles of an oncolytic virus for glioblastoma.
abstract: Glioblastoma multiforme (GBM) accounts for the majority of primary malignant brain tumors and remains virtually incurable despite extensive surgical resection, radiotherapy, and chemotherapy. Treatment difficulty is due to its exceptional infiltrative nature and proclivity to integrate into normal brain tissue. Long-term survivors are rare, and median survival for patients is about 1 year. Use of adult stem cells as cellular delivery vehicles for anticancer agents is a novel attractive therapeutic strategy. We hypothesized that adipose-derived stem cells (ADSCs) possess the ability to home and deliver myxoma virus to glioma cells and experimental gliomas. We infected ADSCs with vMyxgfp and found them to be permissive for myxoma virus replication. ADSCs supported single and multiple rounds of replication leading to productive infection. Further, we observed no significant impact on ADSC viability. We cocultured fluorescently labeled GBM cells with myxoma virus-infected ADSCs in three-dimensional assay and observed successful cross infection and concomitant cell death almost exclusively in GBM cells. In vivo orthotopic studies injected with vMyxgfp-ADSCs intracranially away from the tumor demonstrated that myxoma virus was delivered by ADSCs resulting in significant survival increase. Our data suggest that ADSCs are promising new carriers of oncolytic viruses, specifically myxoma virus, to brain tumors.
authors.affiliation: Brain Tumor Center of Excellence, Department of Neurosurgery, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
authors.forename: Darnell T
authors.initials: DT
authors.lastname: Josiah
authors.forename: Dongqin
authors.initials: D
authors.lastname: Zhu
authors.forename: Fernanda
authors.initials: F
authors.lastname: Dreher
authors.forename: John
authors.initials: J
authors.lastname: Olson
authors.forename: Grant
authors.initials: G
authors.lastname: McFadden
authors.forename: Hannah
authors.initials: H
authors.lastname: Caldas
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D005260:Female; D005470:Fluorometry; D005909:Glioblastoma / Q000628:therapy*; D006801:Humans; D008279:Magnetic Resonance Imaging; D051379:Mice; D008819:Mice, Nude; D009233:Myxoma virus / Q000235:genetics / Q000502:physiology; D050130:Oncolytic Virotherapy / Q000379:methods; D050504:Oncolytic Viruses / Q000235:genetics / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*