Baculovirus-transduced bone marrow mesenchymal stem cells for systemic cancer therapy

Bak, Xiao Ying; Yang, Jianbo; Wang, S

doi:10.1038/cgt.2010.32

Cited by 42 publications

(36 citation statements)

References 38 publications

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“…24,25,27,42 Viruses were produced and propagated in Sf9 insect cells according to the manual of Bac-to-Bac Baculovirus Expression System (Invitrogen). Budded viruses in the insect cell-culture medium were centrifuged at 2000 g for 10 min to remove cell debris, and concentrated by a second round of centrifugation at 28 000 g for 60 min.…”

Section: Baculovirus Preparation and Cell Transductionmentioning

confidence: 99%

“…These cells were generated as described 27 and maintained with 500 mg ml À1 geneticin. U87-luc cells (1Â10 5 cells in 1 ml PBS) were injected into the right hemisphere in nude mice as described above.…”

Section: Animal Studies To Evaluate Therapeutic Efficacymentioning

confidence: 99%

“…[19][20][21][22][23] Baculovirus-derived vectors are capable of transducing both dividing and non-dividing cells including human embryonic stem cells (hESCs) 24,25 and mesenchymal stem cells. 26,27 The great potential of NSCs in cancer therapy highlights the need for consistent and renewable sources for the collection or production of uniform human NSCs suitable for clinical applications. Fetal or adult human brain tissues provide one possible source of primary human NSCs.…”

Section: Introductionmentioning

confidence: 99%

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RETRACTED ARTICLE: Targeted suicide gene therapy for glioma using human embryonic stem cell-derived neural stem cells genetically modified by baculoviral vectors

et al. 2011

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Tumor-tropic neural stem cells (NSCs) can be used in the Trojan horse approach as cellular vehicles for targeted delivery of therapeutic agents to distant tumor sites. To realize this cancer therapy potential, it is important to have a renewable source to generate large quantities of uniform human NSCs. Here, we reported that NSCs derived from HES1 human embryonic stem cell line were capable of migrating into intracranial glioma xenografts after systemic injection or after intracranial injection at a site distant from the tumor. To test whether the HES1-derived NSCs can be used for cancer gene therapy, we used a baculoviral vector to introduce the herpes simplex virus thymidine kinase suicide gene into the cells and demonstrated that baculovirusmediated transgene expression may last for at least 3 weeks in NSCs. After being injected into the cerebral hemisphere opposite the tumor site and in the presence of ganciclovir, NSCs expressing the suicide gene were able to inhibit the growth of human glioma xenografts and prolong survival of tumor-bearing mice. Our findings suggest that human embryonic stem cells could potentially serve as a clinically viable source for production of cellular vehicles suitable for targeted anticancer gene therapy.

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Section: Baculovirus Preparation and Cell Transductionmentioning

confidence: 99%

Section: Animal Studies To Evaluate Therapeutic Efficacymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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RETRACTED ARTICLE: Targeted suicide gene therapy for glioma using human embryonic stem cell-derived neural stem cells genetically modified by baculoviral vectors

et al. 2011

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“…Migratory stem cell vectors have been introduced to achieve improved intratumoral distribution of the prodrug-converting enzyme. In vivo preclinical studies confirming the feasibility of this approach for the treatment of glioma have been conducted using NSCs (17,44,83) and MSCs (81,(84)(85)(86)(87)(88)(89)(90) as HSV-tk delivery vehicles. It has also been proven that the 'bystander effect' of HSV-tk/GCV suicide gene therapy does not damage normal brain tissues (91).…”

Section: Enzyme/prodrug-based Therapy ('Suicide' Gene Therapy)mentioning

confidence: 99%

Use of genetically engineered stem cells for glioma therapy

2015

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Abstract. Glioblastoma, the most common and most malignant type of primary brain tumor, is associated with poor prognosis, even when treated using combined therapies, including surgery followed by concomitant radiotherapy with temozolomide-based chemotherapy. The invasive nature of this type of tumor is a major reason underlying treatment failure. The tumor-tropic ability of neural and mesenchymal stem cells offers an alternative therapeutic approach, where these cells may be used as vehicles for the invasion of tumors. Stem cell-based therapy is particularly attractive due to its tumor selectivity, meaning that the stem cells are able to target tumor cells without harming healthy brain tissue, as well as the extensive tumor tropism of stem cells when delivering anti-tumor substances, even to distant tumor microsatellites. Stem cells have previously been used to deliver cytokine genes, suicide genes and oncolytic viruses. The present review will summarize current trends in experimental studies of stem cell-based gene therapy against gliomas, and discuss the potential concerns for translating these promising strategies into clinical use.

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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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Baculovirus-transduced bone marrow mesenchymal stem cells for systemic cancer therapy

Cited by 42 publications

References 38 publications

RETRACTED ARTICLE: Targeted suicide gene therapy for glioma using human embryonic stem cell-derived neural stem cells genetically modified by baculoviral vectors

RETRACTED ARTICLE: Targeted suicide gene therapy for glioma using human embryonic stem cell-derived neural stem cells genetically modified by baculoviral vectors

Use of genetically engineered stem cells for glioma therapy

Current Status of Gene Therapy for Brain Tumors∗

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