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A New Approach in Gene Therapy of Glioblastoma Multiforme: Human Olfactory Ensheathing Cells as a Novel Carrier for Suicide Gene Delivery

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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.

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Acknowledgments

This study was supported by grant number 20035 obtained from School of Advanced Technologies in Medicine and grant 19925 from Brain and Spinal Cord injury Research Center, Tehran University of Medical Sciences.

Conflict of Interest

The authors declare no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Neuroscience, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Mansoureh Hashemi & Mahmoudreza Hadjighassem

  2. Systems and Synthetic Biology Group, Mede Bioeconomy Company, Tehran, Iran

    Ali Fallah

  3. cGMP-Compliant Stem Cell Manufacturing Facility, Brain and Spinal Cord Injury Research Center, Tehran University of Medical Sciences, Tehran, Iran

    Hamid Reza Aghayan & Babak Arjmand

  4. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Research Institute, Tehran University of Medical Sciences, Tehran, Iran

    Hamid Reza Aghayan & Babak Arjmand

  5. Otorhinolaryngology Research Center, Amir-Alam Hospital, Tehran University of Medical Sciences, Tehran, Iran

    Nasrin Yazdani

  6. Applied Cell Sciences Department, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Javad Verdi

  7. Research Center for Science and Technology in Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Javad Verdi

  8. Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran

    Seyed Mohammad Ghodsi, Seyed Mojtaba Miri & Mahmoudreza Hadjighassem

  9. Department of Neurosurgery, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran

    Seyed Mojtaba Miri

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  1. Mansoureh Hashemi
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  2. Ali Fallah
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  9. Mahmoudreza Hadjighassem
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Correspondence to Mahmoudreza Hadjighassem.

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Hashemi, M., Fallah, A., Aghayan, H.R. et al. A New Approach in Gene Therapy of Glioblastoma Multiforme: Human Olfactory Ensheathing Cells as a Novel Carrier for Suicide Gene Delivery. Mol Neurobiol 53, 5118–5128 (2016). https://doi.org/10.1007/s12035-015-9412-y

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  • DOI: https://doi.org/10.1007/s12035-015-9412-y

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