Use of Mesenchymal Stem Cells for Gene Delivery to Intracranial Glioma

Virus-mediated gene therapies against brain tumors have been limited by the difficulty in tracking glioma cells infiltrating the brain parenchyma. Mesenchymal stem cells (MSCs) are particularly attractive cells for clinical use in cell-based therapies because they have tumor-targeting properties, can be easily isolated and expanded to the numbers required for use, and can be genetically manipulated with viral vectors. In addition, most of the replication-deficient adenoviral vectors that have been used to transduce MSCs are based on human Ad serotype 5 (Ad5). However, transduction of MSCs by conventional Ad5 vectors is inefficient, even when very high multiplicities of infection are used because MSCs do not express the cellular coxsackie-adenovirus receptor. This chapter describes in detail how such adenoviral transduction of MSCs mediated by cell-permeable peptides should be prepared and handled, and applied for the use of targeted therapeutic gene delivery into glioma by an in vitro migration assay and by in vivo injection of MSCs into the tumor mass or the opposite hemisphere of established human glioma in nude mice.