genetically engineered multilineage-differentiating stress-enduring cells as cellular vehicles against malignant gliomas

Clicks: 233
ID: 255745
2017
Malignant glioma, the most common malignant brain tumor in adults, is difficult to treat due to its aggressive invasive nature. Enzyme/prodrug suicide gene therapy based on the herpes simplex virus thymidine kinase (HSVtk)/ganciclovir (GCV) system is an efficient strategy for treating malignant gliomas. In the present study, we evaluated treatment with multilineage-differentiating stress-enduring (Muse) cells, which are endogenous non-tumorigenic pluripotent-like stem cells that are easily collectable from the bone marrow as SSEA-3+ cells, as carriers of the HSVtk gene. Human Muse cells showed potent migratory activity toward glioma cells both in vitro and in vivo. HSVtk gene-transduced Muse cells (Muse-tk cells) at a cell number of only 1/32 that of U87 human glioma cells completely eradicated U87 gliomas in nude mouse brains, showing a robust in vivo bystander effect. Pre-existing intracranial U87 gliomas in nude mouse brains injected intratumorally with Muse-tk cells followed by intraperitoneal GCV administration were significantly reduced in size within 2 weeks, and 4 of 10 treated mice survived over 200 days. These findings suggest that intratumoral Muse-tk cell injection followed by systemic GCV administration is safe and effective and that allogeneic Muse-tk cell-medicated suicide gene therapy for malignant glioma is clinically feasible.
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Authors ;Tomohiro Yamasaki;Shohei Wakao;Hiroshi Kawaji;Shinichiro Koizumi;Tetsuro Sameshima;Mari Dezawa;Hiroki Namba
Journal neurology india
Year 2017
DOI 10.1016/j.omto.2017.06.001
URL
http://www.sciencedirect.com/science/article/pii/S2372770517300268
Keywords
Migration glioma oncology gene therapy tumors Oncology including cancer and carcinogens tumors including cancer and carcinogens stem cellsneoplasms

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