Suicide gene therapy mediated by mesenchymal stem cells with their ability to engraft into
tumors makes these therapeutic stem cells an attractive tool to activate
prodrugs directly within the
tumor mass. In this study, we evaluated the therapeutic efficacy of human mesenchymal stem cells derived from bone marrow and from adipose tissue, engineered to express the suicide gene
cytosine deaminase::
uracil phosphoribosyltransferase to treat intracerebral rat C6
glioblastoma in a simulated clinical therapeutic scenario. Intracerebrally grown
glioblastoma was treated by resection and subsequently with single or repeated intracerebral inoculations of therapeutic stem cells followed by a continuous intracerebroventricular delivery of
5-fluorocytosine using an osmotic pump. Kaplan-Meier survival curves revealed that surgical resection of the
tumor increased the survival time of the resected animals depending on the extent of surgical intervention. However, direct
injections of therapeutic stem cells into the brain tissue surrounding the postoperative resection cavity led to a curative outcome in a significant number of treated animals. Moreover, the continuous supply of therapeutic stem cells into the brain with growing
glioblastoma by osmotic pumps together with continuous
prodrug delivery also proved to be therapeutically efficient. We assume that observed curative
therapy of
glioblastoma by stem cell-mediated
prodrug gene therapy might be caused by the destruction of both
tumor cells and the niche where
glioblastoma initiating cells reside.