title: Stem cell-mediated gene therapies for malignant gliomas: a promising targeted therapeutic approach?
abstract: Glioblastomas are aggressive intrinsic brain tumors. The median overall survival does not exceed 15 months despite surgical resection, radiotherapy, and chemotherapy even in selected clinical trial populations. One reason for this poor outcome is the characteristic infiltrative growth pattern of glioblastomas with tumor cells deeply infiltrating into the normal brain parenchyma and thereby escaping surgical debulking and involved-field radiation therapy. Novel therapeutic strategies are urgently needed including those that target disseminated tumor cells, too. In this regard, the application of adult stem cells as cellular vehicles for the delivery of therapeutic molecules has emerged during the last decade as an experimental approach. Adult stem cells with a tropism for gliomas include neural stem and progenitor cells, mesenchymal stem cells, hematopoietic progenitor cells, and endothelial progenitor cells. Importantly, these candidate cellular carriers also localize to sites of hypoxia and invasive tumor borders which are usually not targeted by currently available therapeutic approaches. Stem cell-based therapeutic approaches could therefore help to overcome some of the current limitations of radio- and chemotherapy and may circumvent toxicity to normal resident cells of the central nervous system. The development of neural stem- and progenitor-based therapies is advanced with a currently ongoing phase I clinical study. We review rationale, achievements, and future challenges in this field.
authors.affiliation: Laboratory of Molecular Neurooncology, University of Zurich, Switzerland.
authors.forename: Ghazaleh
authors.initials: G
authors.lastname: Tabatabai
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wick
authors.forename: Michael
authors.initials: M
authors.lastname: Weller
mesh_terms: D000818:Animals; D015316:Genetic Therapy / Q000379:methods*; D005910:Glioma / Q000628:therapy*; D006801:Humans; D051379:Mice; D033581:Stem Cell Transplantation / Q000379:methods*