title: Combination of the multipotent mesenchymal stromal cell transplantation with administration of temozolomide increases survival of rats with experimental glioblastoma.
abstract: Glioblastoma multiforme (GM) is an aggressive malignant tumor of the brain. The standard treatment of GM is surgical resection with consequent radio- and chemotherapy with temozolomide. The prognosis is unfavorable, with a survival time of 12-14 months. The phenomenon of targeted migration to the tumor in the brain opens novel possibilities for the treatment of GM. Multipotent mesenchymal stromal cells (MMSCs) are a cell type with anti-carcinogenic properties and can be used to optimize GM therapy. The aim of the present study was to investigate the effects of MMSC transplantation in the chemotherapy of a rat model of C6 glioma. A total of 130 animals were divided into a control group, a temozolomide group, MMSCs group and temozolomide + MMSCs group. The experiment was performed over 70 days, and a combination of molecular biology, surgical and neuroimaging techniques, as well as histological and physiological examinations was used. Tumor size was smallest in the temozolomide (115.76 ± 16.25 mm(3)) and in temozolomide + MMSCs (114.74 ± 5.54 mm(3)) groups, which was significantly smaller than the neoplastic node size in the control group (202.09 ± 39.72 mm(3)) (P<0.05). The animals in the temozolomide + MMSCs group showed significantly higher survival rates in comparison with those in the control and temozolomide groups. The MMSCs migrated from the site of implantation to the neoplastic focus and interacted with glioma cells; however, the mechanism requires further research. In conclusion, MMSC transplantation combined with temozolomide treatment significantly extended the survival of experimental animals in comparison with those treated with temozolomide only.
authors.affiliation: Laboratory of Molecular and Cellular Neurobiology, School of Biomedicine, Far Eastern Federal University, Vladivostok 690091, Russian Federation.
authors.forename: Igor
authors.initials: I
authors.lastname: Bryukhovetskiy
authors.affiliation: NeuroVita Clinic of Restorative Interventional Therapy and Neurology, Moscow 115478, Russian Federation.
authors.forename: Andrei
authors.initials: A
authors.lastname: Bryukhovetsky
authors.affiliation: Laboratory of Molecular and Cellular Neurobiology, School of Biomedicine, Far Eastern Federal University, Vladivostok 690091, Russian Federation.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Khotimchenko
authors.affiliation: Laboratory of Molecular and Cellular Neurobiology, School of Biomedicine, Far Eastern Federal University, Vladivostok 690091, Russian Federation.
authors.forename: Polina
authors.initials: P
authors.lastname: Mischenko
authors.affiliation: Laboratory of Molecular and Cellular Neurobiology, School of Biomedicine, Far Eastern Federal University, Vladivostok 690091, Russian Federation.
authors.forename: Elena
authors.initials: E
authors.lastname: Tolok
authors.affiliation: Laboratory of Pharmacology, A.V. Zhirmunski Institute of Marine Biology Far Eastern Branch Russian Academy of Science, Vladivostok 690041, Russian Federation.
authors.forename: Rodion
authors.initials: R
authors.lastname: Khotimchenko
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004195:Disease Models, Animal; D005909:Glioblastoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology; D051381:Rats; D017208:Rats, Wistar; D015996:Survival Rate; D000077204:Temozolomide; D014184:Transplantation, Homologous
chemical_list: D003606:Dacarbazine; D000077204:Temozolomide