title: Human embryonic stem cell-derived mesenchymal stem cells as cellular delivery vehicles for prodrug gene therapy of glioblastoma.
abstract: Mesenchymal stem cells (MSCs) possess tumor-tropic properties and consequently have been used to deliver therapeutic agents for cancer treatment. Their potential in cancer therapy highlights the need for a consistent and renewable source for the production of uniform human MSCs suitable for clinical applications. In this study, we seek to investigate whether human embryonic stem cells can be used as a cell source to fulfill this goal. We generated MSC-like cells from two human embryonic stem cell lines, HuES9 and H1, and observed that MSC-like cells derived from human embryonic stem cells were able to migrate into human glioma intracranial xenografts after being injected into the cerebral hemisphere contralateral to the tumor inoculation site. We engineered these cells with baculoviral and lentiviral vectors, respectively, for transient and stable expression of the herpes simplex virus thymidine kinase gene. In tumor-bearing mice the engineered MSC-like cells were capable of inhibiting tumor growth and prolonging survival in the presence of ganciclovir after they were injected either directly into the xenografts or into the opposite hemisphere. Our findings suggest that human embryonic stem cell-derived MSCs may be a viable and attractive alternative for large-scale derivation of targeting vehicles for cancer therapy.
authors.affiliation: Institute of Bioengineering and Nanotechnology, Singapore 117602, Singapore.
authors.forename: Xiao Ying
authors.initials: XY
authors.lastname: Bak
authors.forename: Dang Hoang
authors.initials: DH
authors.lastname: Lam
authors.forename: Jingye
authors.initials: J
authors.lastname: Yang
authors.forename: Kai
authors.initials: K
authors.lastname: Ye
authors.forename: Esther Lee Xing
authors.initials: EL
authors.lastname: Wei
authors.forename: Sai Kiang
authors.initials: SK
authors.lastname: Lim
authors.forename: Shu
authors.initials: S
authors.lastname: Wang
mesh_terms: D000818:Animals; D016367:Baculoviridae / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement; D053595:Embryonic Stem Cells / Q000166:cytology*; D005240:Feasibility Studies; D015774:Ganciclovir / Q000627:therapeutic use; D005822:Genetic Vectors; D005909:Glioblastoma / Q000235:genetics / Q000628:therapy*; D006564:Herpesviridae; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011355:Prodrugs / Q000008:administration & dosage*; D013937:Thymidine Kinase / Q000235:genetics*; D014764:Viral Proteins / Q000235:genetics*
chemical_list: D011355:Prodrugs; D014764:Viral Proteins; D013937:Thymidine Kinase; D015774:Ganciclovir