title: A New Approach in Gene Therapy of Glioblastoma Multiforme: Human Olfactory Ensheathing Cells as a Novel Carrier for Suicide Gene Delivery.
abstract: Olfactory ensheathing cells (OECs) of human olfactory mucosa are a type of glial-like cells that possess good migratory and tropism properties. We believe that neuronal-derived vehicle may have better capability to receive to the site of injury. In addition to, obtaining of such vehicle from the patient reduces risk of unwanted complications. So, in this study, we investigate whether human olfactory ensheathing cells can be used as a cell source for the first time in gene delivery to assay the tumoricidal effect of herpes simplex virus thymidine kinase gene (HSV-tk) on glioblastoma multiforme (GBM). We obtained OECs from superior turbinate of human nasal cavity mucosa, and cell phenotype was confirmed by the expression of cell-specific antigens including low-affinity nerve growth factor receptor (p75 neurotrophin receptor), microtubule-associated protein-2 (MAP2), and S100 calcium binding protein B (S100-beta) using immunocytochemistry. Then, these cells were transduced by lentiviral vector for transient and stable expression of the herpes simplex virus thymidine kinase gene (OEC-tk). The migratory capacity of OEC-tk, their potency to convert prodrug ganciclovir to toxic form, and cytotoxic effect on astrocyte cells were assayed in vitro. The OECs showed fibroblast-like morphology and expressed specific antigens such as p75 neurotrophin receptor, S100-beta, and MAP2. Our results indicated that OECs-tk were able to migrate toward primary cultured human glioblastoma multiforme and affected survival rate of tumor cells according to exposure time and concentration of ganciclovir. Also, OECs-HSV-tk was capable of inducing apoptosis in tumor cells. Our findings suggest that human OECs could employ as a possible tool to transfer anticancer agent in gene therapy of brain tumor.
authors.affiliation: Department of Neuroscience, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mansoureh
authors.initials: M
authors.lastname: Hashemi
authors.affiliation: Systems and Synthetic Biology Group, Mede Bioeconomy Company, Tehran, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Fallah
authors.affiliation: cGMP-Compliant Stem Cell Manufacturing Facility, Brain and Spinal Cord Injury Research Center, Tehran University of Medical Sciences, Tehran, Iran.|Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Hamid Reza
authors.initials: HR
authors.lastname: Aghayan
authors.affiliation: cGMP-Compliant Stem Cell Manufacturing Facility, Brain and Spinal Cord Injury Research Center, Tehran University of Medical Sciences, Tehran, Iran.|Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Babak
authors.initials: B
authors.lastname: Arjmand
authors.affiliation: Otorhinolaryngology Research Center, Amir-Alam Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Nasrin
authors.initials: N
authors.lastname: Yazdani
authors.affiliation: Applied Cell Sciences Department, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.|Research Center for Science and Technology in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Javad
authors.initials: J
authors.lastname: Verdi
authors.affiliation: Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Seyed Mohammad
authors.initials: SM
authors.lastname: Ghodsi
authors.affiliation: Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.|Department of Neurosurgery, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Seyed Mojtaba
authors.initials: SM
authors.lastname: Miri
authors.affiliation: Department of Neuroscience, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran. mhadjighssem@tums.ac.ir.|Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran. mhadjighssem@tums.ac.ir.
authors.forename: Mahmoudreza
authors.initials: M
authors.lastname: Hadjighassem
mesh_terms: D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D024201:Bystander Effect / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D048430:Cell Shape; D015774:Ganciclovir / Q000494:pharmacology / Q000627:therapeutic use; D018014:Gene Transfer Techniques; D041722:Genes, Transgenic, Suicide; D015316:Genetic Therapy; D005909:Glioblastoma / Q000188:drug therapy / Q000235:genetics* / Q000628:therapy*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D009830:Olfactory Bulb / Q000473:pathology*; D010641:Phenotype; D013937:Thymidine Kinase / Q000378:metabolism
chemical_list: D049452:Green Fluorescent Proteins; D013937:Thymidine Kinase; D015774:Ganciclovir
keywords: Cell migration; Gene therapy; Glioblastoma multiforme; Olfactory ensheathing cells; Vehicle