Human Embryonic Stem Cell-Derived Mesenchymal Stem Cells as Cellular Delivery Vehicles for Prodrug Gene Therapy of Glioblastoma

Bak, Xiao Ying; Dang, Hoang Lam; Yang, Jianbo; Yang, Kai; Lee, Esther X.W.; Lim, Sai Kiang; Wang, Shu

doi:10.1089/hum.2010.212

Cited by 54 publications

(40 citation statements)

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“…These attributes have prompted the development of BV vectors for in vitro and in vivo gene delivery (3), RNA interference (4), cell-based assay development (5), production of viral vectors (6) and recombinant proteins (7), as well as cartilage and bone tissue engineering (8). Beyond these applications, BV is also used as an expression vector for the treatment of various cancers, including hepatoma (9), melanoma (10), colon cancer (11), brain cancer (12)(13)(14)(15)(16), prostate cancer (17,18), and ovarian cancer (17). In addition, BV has been explosively developed as a vaccine expression/display vector against a variety of pathogens, including avian influenza virus (AIV) (19)(20)(21)(22), avian reovirus (23), pseudorabies virus (24), enterovirus 71 (25), Plasmodium berghei (26), and many others (for a review, see reference 1).…”

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confidence: 99%

Adaptive Immune Responses Elicited by Baculovirus and Impacts on Subsequent Transgene Expression In Vivo

Luo

Lin

et al. 2013

J Virol

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mentioning

confidence: 99%

Adaptive Immune Responses Elicited by Baculovirus and Impacts on Subsequent Transgene Expression In Vivo

Luo

Lin

et al. 2013

J Virol

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“…Other types of adult stem cells, such as mesenchymal stem cells (MSCs) and neural stem cells (NSCs), as well as MSCs and NSCs derived from pluripotent stem cells, also show the ability to home to tumors [17,[32][33][34][35]. However, it has been noted that MSCs that reach tumor stroma can contribute to tumor development through the mechanisms of creating a niche to support cancer stem cells, promoting angiogenesis, and/or promoting cancer metastasis [36][37][38].…”

Section: Discussionmentioning

confidence: 99%

Antitumor Effects of CD40 Ligand-Expressing Endothelial Progenitor Cells Derived From Human Induced Pluripotent Stem Cells in a Metastatic Breast Cancer Model

Purwanti

Chen

Lam

et al. 2014

Stem Cells Translational Medicine

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Given their intrinsic ability to home to tumor sites, endothelial progenitor cells (EPCs) are attractive as cellular vehicles for targeted cancer gene therapy. However, collecting sufficient EPCs is one of the challenging issues critical for effective clinical translation of this new approach. In this study, we sought to explore whether human induced pluripotent stem (iPS) cells could be used as a reliable and accessible cell source to generate human EPCs suitable for cancer treatment. We used an embryoid body formation method to derive CD133 + CD34+ EPCs from human iPS cells. The generated EPCs expressed endothelial markers such as CD31, Flk1, and vascular endothelial-cadherin without expression of the CD45 hematopoietic marker. After intravenous injection, the iPS cell-derived EPCs migrated toward orthotopic and lung metastatic tumors in the mouse 4T1 breast cancer model but did not promote tumor growth and metastasis. To investigate their therapeutic potential, the EPCs were transduced with baculovirus encoding the potent T cell costimulatory molecule CD40 ligand. The systemic injection of the CD40 ligand-expressing EPCs stimulated the secretion of both tumor necrosis factor-a and interferon-g and increased the caspase 3/7 activity in the lungs with metastatic tumors, leading to prolonged survival of the tumor bearing mice. Therefore, our findings suggest that human iPS cell-derived EPCs have the potential to serve as tumor-targeted cellular vehicles for anticancer gene therapy. STEM CELLS TRANSLATIONAL MEDICINE 2014;3:923-935

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“…[134][135][136] Different viral vectors have been used to transduce MSCs including, retrovirus, lentivirus, adenovirus, and baculovirus. 137,138 A number of suicide genes (TK, CD, rCE) have been introduced into MSCs and shown to be effective with prodrug in treating intracranial glioma models [139][140][141][142][143] (Table IV). Unfortunately, some of these studies were performed by coimplanting the MSCs with the glioma cell lines, 142,144 which obviates the migratory advantage of this strategy.…”

Section: Cytotoxic or Suicide Gene/prodrug Therapymentioning

confidence: 99%

Current Status of Gene Therapy for Brain Tumors∗

Ning

Rabkin

2015

Translating Gene Therapy to the Clinic

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Glioblastoma (GBM) is the most common and deadliest primary brain tumor in adults, with current treatments having limited impact on disease progression. Therefore the development of alternative treatment options is greatly needed. Gene therapy is a treatment strategy that relies on the delivery of genetic material, usually transgenes or viruses, into cells for therapeutic purposes, and has been applied to GBM with increasing promise. We have included selectively replicationcompetent oncolytic viruses within this strategy, although the virus acts directly as a complex biologic anti-tumor agent rather than as a classic gene delivery vehicle. GBM is a good candidate for gene therapy because tumors remain locally within the brain and only rarely metastasize to other tissues; the majority of cells in the brain are post-mitotic, which allows for specific targeting of dividing tumor cells; and tumors can often be accessed neurosurgically for administration of therapy. Delivery vehicles used for brain tumors include nonreplicating viral vectors, normal adult stem/progenitor cells, and oncolytic viruses. The therapeutic transgenes or viruses are typically cytotoxic or express prodrug activating suicide genes to kill glioma cells, immunostimulatory to induce or amplify anti-tumor immune responses, and/or modify the tumor microenvironment such as blocking angiogenesis. This review describes current preclinical and clinical gene therapy strategies for the treatment of glioma.Treating malignant gliomas, of which glioblastoma (GBM) is the most common and least curable, remains a daunting challenge even after substantial efforts to develop alternative therapies. The current standard of care is maximal surgical resection followed by radiation and temozolomide chemotherapy; however, the median survival still remains less than 15 months. 1,2 This poor survival is due to the aggressive and invasive nature of the tumor cells, resistance to treatment, and the challenges of delivering therapeutics into the brain. 3 GBM is thought to be derived from a small population of glioblastoma stem cells (GSCs), so-called because of their stem cell-like properties of self-renewal and multilineage differentiation while being highly tumorigenic. [4][5][6] GSCs have become an important model for studying GBM because their xenografts mimic the heterogeneous histopathology of the patient's tumor from which they were derived 7,8 and they remain genotypically similar to the patient's tumor, in contrast to serum-cultured cell lines. 9 These cells have provided insights into the origin of tumor-initiating cells and new targets for therapy. Other GBM animal models include established glioma cell lines (human and rodent) implanted intracranially into immunodeficient or immunocompetent animals, and genetically engineered mice that spontaneously develop brain tumors or are induced with viral vectors. 10 GENE DELIVERY VEHICLES FOR GLIOBLASTOMAMost gene therapies for GBM use biologic vectors such as viruses or cells. Replicationdefective or non-repli...

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Human Embryonic Stem Cell-Derived Mesenchymal Stem Cells as Cellular Delivery Vehicles for Prodrug Gene Therapy of Glioblastoma

Cited by 54 publications

References 50 publications

Adaptive Immune Responses Elicited by Baculovirus and Impacts on Subsequent Transgene Expression In Vivo

Adaptive Immune Responses Elicited by Baculovirus and Impacts on Subsequent Transgene Expression In Vivo

Antitumor Effects of CD40 Ligand-Expressing Endothelial Progenitor Cells Derived From Human Induced Pluripotent Stem Cells in a Metastatic Breast Cancer Model

Current Status of Gene Therapy for Brain Tumors∗

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