Baculovirus transduction of human mesenchymal stem cell-derived progenitor cells: variation of transgene expression with cellular differentiation states

Yc, Ho; Hp, Lee; Sm, Hwang; Wh, Lo; Hc, Chen; Chung, Chun Kee; Hu, Yue

doi:10.1038/sj.gt.3302796

Cited by 45 publications

(55 citation statements)

References 40 publications

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“…Baculoviral vectors have been successfully used for transduction of human bone marrow MSCs. [17][18][19] After transplantation of baculovirustransduced MSCs into allogeneic animals, there was no obvious cell clearance, as judged by the persistence of transplanted cells and absence of CD8 þ T cells infiltration, 19 suggesting the potential and safety of in vivo applications of baculovirus-transduced MSCs for cell-based gene therapy. In an effort to test tissue engineering by gene delivery, MSCs genetically modified ex vivo by baculoviral vectors were able to induce ectopic bone formation and repair osteochondral defects in animals.…”

Section: Introductionmentioning

confidence: 99%

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

2010

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Adult stem cells may serve as powerful cellular vehicles to deliver therapeutic genes for cancer therapy. In such applications, effective and safe transduction to load stem cells with genes of interest is essential. To examine whether baculovirus can be used to fulfill this task, we tested a range of baculoviral vectors in human bone marrow mesenchymal stem cells (MSCs). A vector using the human cytomegalovirus immediate-early gene promoter to drive transgene expression and the woodchuck hepatitis virus posttranscriptional regulatory element to enhance translation was able to transduce MSCs with efficiency close to 80%. Following the observation that baculoviral transduction did not significantly affect surface marker expression of the stem cells, we tested the feasibility of using baculovirus-transduced MSCs for targeted cancer therapy. We transduced cells with a baculoviral vector harboring the herpes simplex virus thymidine kinase gene, and performed tail vein injection of the transduced cells into mice preinoculated subcutaneously with human U87 glioma cells. After ganciclovir prodrug injection, we observed inhibition of tumor growth and significantly prolonged survival of tumor-inoculated animals. Our findings suggest that baculoviral transduction of MSCs is an attractive option to generate targeting vehicles for systemic cancer therapy.

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Section: Introductionmentioning

confidence: 99%

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

2010

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“…[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%

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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“…Among these three lineages, the permissiveness of osteogenic progenitors to baculovirus transduction is relatively independent of the differentiation status and the transduction efficiency remains nearly 60% for hMSCs differentiating along the osteogenic lineage for 4 weeks. 20 Very importantly, baculovirus transduction itself does not obstruct the differentiation capacity of hMSCs. 20 These data indicate that hMSCs and hMSCs-derived osteogenic progenitors are highly susceptible to baculovirus transduction, thus implicating the possibilities of genetically modifying these cells for tissue engineering.…”

Section: Introductionmentioning

confidence: 99%

“…20 Very importantly, baculovirus transduction itself does not obstruct the differentiation capacity of hMSCs. 20 These data indicate that hMSCs and hMSCs-derived osteogenic progenitors are highly susceptible to baculovirus transduction, thus implicating the possibilities of genetically modifying these cells for tissue engineering.…”

Section: Introductionmentioning

confidence: 99%

“…Prompted by the potential of MSCs for cell therapy and baculovirus for gene delivery, we have demonstrated that human MSCs (hMSCs) derived from bone marrow can be transduced by baculovirus at an efficiency of up to 76%. 20 Furthermore, adipogenic, chondrogenic and osteogenic progenitors originating from hMSCs can be transduced by baculovirus, and the transgene (EGFP) expression level and duration rest heavily on the differentiation states at which the committed progenitors are transduced. Among these three lineages, the permissiveness of osteogenic progenitors to baculovirus transduction is relatively independent of the differentiation status and the transduction efficiency remains nearly 60% for hMSCs differentiating along the osteogenic lineage for 4 weeks.…”

Section: Introductionmentioning

confidence: 99%

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Baculovirus as a new gene delivery vector for stem cell engineering and bone tissue engineering

et al. 2007

Gene Ther

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Baculovirus has emerged as a novel vector for in vitro and in vivo gene delivery due to its low cytotoxicity and nonreplication nature in mammalian cells, but the applications of baculovirus in the genetic modification of human mesenchymal stem cells (hMSCs) and tissue engineering are yet to be reported. In this study, we genetically engineered hMSCs with a baculovirus (Bac-CB) expressing bone morphogenetic protein-2 (BMP-2). Bac-CB transduction of hMSCs at a multiplicity of infection of 40 triggered effective differentiation of hMSCs into osteoblasts. Supertransduction at day 6 after initial transduction enhanced the BMP-2 expression and further accelerated the in vitro osteogenesis, as confirmed by alkaline phosphatase assay, Alizarin red staining and reverse transcription-polymerase chain reaction analysis of osteoblastic genes. Implantation of the supertransduced cells at ectopic sites in the nude mice resulted in efficient cell differentiation into osteoblasts at week 2 and induced progressive mineralization and partial bone formation at week 6, as confirmed by hematoxylin and eosin, immunohistochemical and Alizarin red staining. These data collectively demonstrated, for the first time, the potential of baculovirus in hMSCs engineering and implicated its use in bone tissue engineering.

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Baculovirus transduction of human mesenchymal stem cell-derived progenitor cells: variation of transgene expression with cellular differentiation states

Cited by 45 publications

References 40 publications

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

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

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

Baculovirus as a new gene delivery vector for stem cell engineering and bone tissue engineering

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