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

作者：Hashemi Mansoureh; Fallah Ali; Aghayan Hamid Reza; Arjmand Babak; Yazdani Nasrin; Verdi Javad; Ghodsi Seyed Mohammad; Miri Seyed Mojtaba; Hadjighassem Mahmoudreza^*

来源：Molecular Neurobiology, 2016, 53(8): 5118-5128.

DOI：10.1007/s12035-015-9412-y

• Olfactory ensheathing cells
• Cell migration
• Gene therapy
• Vehicle
• Glioblastoma multiforme

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.

• 出版日期2016-10