Baculovirus-transduced bone marrow mesenchymal stem cells for systemic cancer therapy.
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.
Bak
X Y
XY
Institute of Bioengineering and Nanotechnology, Singapore, Singapore.
Yang
J
J
Wang
S
S
D000818:Animals; D016367:Baculoviridae / Q000235:genetics*; D001853:Bone Marrow / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D017781:Genes, Immediate-Early; D041722:Genes, Transgenic, Suicide; D005822:Genetic Vectors; D005910:Glioma / Q000378:metabolism / Q000628:therapy*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism* / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009423:Nervous System Neoplasms / Q000378:metabolism / Q000628:therapy*; D014161:Transduction, Genetic; D023041:Xenograft Model Antitumor Assays