Bone Marrow-Derived Mesenchymal Stem Cell-Mediated Dual-Gene Therapy for Glioblastoma. 2019

Shuo Shi, and Min Zhang, and Rui Guo, and Ying Miao, and Biao Li
Department of Nuclear Medicine, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.

Bone-marrow mesenchymal stem cells (BMSCs) have been used for systemic delivery of therapeutic genes to solid tumors. However, the optimal treatment time post-BMSC implantation and the assessment of the long-term fate of therapeutic BMSCs post-tumor treatment are critical if such promising therapies are to be translated into clinical practice. An efficient BMSC-based therapeutic strategy has been developed that simultaneously allows killing of tumor cells, inhibiting of tumor angiogenesis, and assessment and eradication of implanted BMSCs after treatment of glioblastoma. BMSCs were engineered to co-express the angiogenesis inhibitor kringle 5 (K5) of human plasminogen, under the control of the cytomegalovirus promoter (CMV) and the human sodium-iodide symporter (NIS), involved in uptake of radioisotopes, under the control of early growth response factor 1 (Egr1), a radiation-activated promoter. A significant decrease in tumor growth and tumor angiogenesis and a subsequent increase in survival were observed when mice bearing glioblastoma were treated with 188Re post-therapeutic intravenous BMSC implantation. Furthermore, the systemic administration of 188Re post-tumor treatment selectively eliminated therapeutic BMSCs expressing NIS, which was monitored in real time by 125I micro single photon emission computed tomography/computed tomography imaging. Meanwhile, the Egr1 promoter induced a 188Re radiation positive feedback effect absorbed by NIS. After intravenous BMSC implantation, BMSCs levels in the tumor and lung both peaked on day 10 and decreased to the lowest levels on days 24 and 17, respectively. These findings suggest that day 17 post-BMSC implantation could be an optimal time for 188Re treatment. These results provide a new adjuvant therapy mediated by BMSCs for glioblastoma treatment.

UI MeSH Term Description Entries
D009928 Organ Specificity Characteristic restricted to a particular organ of the body, such as a cell type, metabolic response or expression of a particular protein or antigen. Tissue Specificity,Organ Specificities,Specificities, Organ,Specificities, Tissue,Specificity, Organ,Specificity, Tissue,Tissue Specificities
D011401 Promoter Regions, Genetic DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes. rRNA Promoter,Early Promoters, Genetic,Late Promoters, Genetic,Middle Promoters, Genetic,Promoter Regions,Promoter, Genetic,Promotor Regions,Promotor, Genetic,Pseudopromoter, Genetic,Early Promoter, Genetic,Genetic Late Promoter,Genetic Middle Promoters,Genetic Promoter,Genetic Promoter Region,Genetic Promoter Regions,Genetic Promoters,Genetic Promotor,Genetic Promotors,Genetic Pseudopromoter,Genetic Pseudopromoters,Late Promoter, Genetic,Middle Promoter, Genetic,Promoter Region,Promoter Region, Genetic,Promoter, Genetic Early,Promoter, rRNA,Promoters, Genetic,Promoters, Genetic Middle,Promoters, rRNA,Promotor Region,Promotors, Genetic,Pseudopromoters, Genetic,Region, Genetic Promoter,Region, Promoter,Region, Promotor,Regions, Genetic Promoter,Regions, Promoter,Regions, Promotor,rRNA Promoters
D011878 Radiotherapy The use of IONIZING RADIATION to treat malignant NEOPLASMS and some benign conditions. Radiotherapy, Targeted,Targeted Radiotherapy,Radiation Therapy,Radiation Therapy, Targeted,Radiation Treatment,Targeted Radiation Therapy,Radiation Therapies,Radiation Therapies, Targeted,Radiation Treatments,Radiotherapies,Radiotherapies, Targeted,Targeted Radiation Therapies,Targeted Radiotherapies,Therapies, Radiation,Therapies, Targeted Radiation,Therapy, Radiation,Therapy, Targeted Radiation,Treatment, Radiation
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D005822 Genetic Vectors DNA molecules capable of autonomous replication within a host cell and into which other DNA sequences can be inserted and thus amplified. Many are derived from PLASMIDS; BACTERIOPHAGES; or VIRUSES. They are used for transporting foreign genes into recipient cells. Genetic vectors possess a functional replicator site and contain GENETIC MARKERS to facilitate their selective recognition. Cloning Vectors,Shuttle Vectors,Vectors, Genetic,Cloning Vector,Genetic Vector,Shuttle Vector,Vector, Cloning,Vector, Genetic,Vector, Shuttle,Vectors, Cloning,Vectors, Shuttle
D005909 Glioblastoma A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures. Astrocytoma, Grade IV,Giant Cell Glioblastoma,Glioblastoma Multiforme,Astrocytomas, Grade IV,Giant Cell Glioblastomas,Glioblastoma, Giant Cell,Glioblastomas,Glioblastomas, Giant Cell,Grade IV Astrocytoma,Grade IV Astrocytomas
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000072098 Single Photon Emission Computed Tomography Computed Tomography An imaging technique using a device which combines TOMOGRAPHY, EMISSION-COMPUTED, SINGLE-PHOTON and TOMOGRAPHY, X-RAY COMPUTED in the same session. CT SPECT,CT SPECT Scan,SPECT CT,SPECT CT Scan,CT SPECT Scans,CT SPECTs,CT Scan, SPECT,CT Scans, SPECT,SPECT CT Scans,SPECT Scan, CT,SPECT Scans, CT,SPECT, CT,SPECTs, CT,Scan, CT SPECT,Scan, SPECT CT,Scans, CT SPECT,Scans, SPECT CT
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015316 Genetic Therapy Techniques and strategies which include the use of coding sequences and other conventional or radical means to transform or modify cells for the purpose of treating or reversing disease conditions. Gene Therapy,Somatic Gene Therapy,DNA Therapy,Gene Therapy, Somatic,Genetic Therapy, Gametic,Genetic Therapy, Somatic,Therapy, DNA,Therapy, Gene,Therapy, Somatic Gene,Gametic Genetic Therapies,Gametic Genetic Therapy,Genetic Therapies,Genetic Therapies, Gametic,Genetic Therapies, Somatic,Somatic Genetic Therapies,Somatic Genetic Therapy,Therapies, Gametic Genetic,Therapies, Genetic,Therapies, Somatic Genetic,Therapy, Gametic Genetic,Therapy, Genetic,Therapy, Somatic Genetic

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