Molecular imaging of stem cell therapy in brain tumors: a step towards personalized medicine.

Abstract

Advances in gene-based medicine since the 1990s have ushered in a new therapeutic strategy of gene therapy for inborn error genetic diseases and also for cancer [1-6]. Personalized treatment strategies using stem, modified or also genetically engineered cells are becoming a reality in clinical medicine. Allogenic or autologous cells can be used for treatment and possibly for early diagnosis of diseases. Hematopoietic, stromal and organ specific stem cells are under evaluation for cell-based therapies, not only for neurological, but also cardiac, pneumological, gynecological, autoimmune and other disorders. Such cell replacement therapy and gene transfer have provided the basis for the development of potentially powerful new therapeutic strategies for a broad spectrum of neurological diseases. However, currently available treatment modalities for brain tumors, including radical surgical resection followed by radiation and chemotherapy, have substantially improved the survival rates [7, 8]; however, a large proportion of patients with brain tumors remain incurable [9]. Therefore, there is substantial need for more effective therapies for patients with malignant brain tumors, and gene therapy targeting brain tumors should fulfill this requirement. Gene therapy for brain tumors includes many therapeutic strategies and these strategies can be subgrouped in two major categories: (i) molecular and (ii) immunologic. The widely used molecular gene therapy approach is suicide gene therapy based on the conversion of non-toxic prodrugs into active anticancer agents via introduction of enzymes, and genetic immunotherapy involves the gene transfer of immune-stimulating cytokines including interleukin (IL)-4, IL-12 and tumor necrosis factor related apoptosis inducing ligand (TRAIL) [10, 11]. For both molecular and immune gene therapy, stem cells can be used as a delivery vehicle of therapeutic genes [12]. Stem cells possess an inherent tumor tropism and have the capacity to target therapeutic genes to tumors, which supports their use as a reliable delivery vehicle to target therapeutic gene products to primary brain tumors and metastatic cancers throughout the brain [13, 14]. The main promise of this emerging technology centers on the potent migratory tropism exhibited by stem cells for disseminated foci of intracranial pathologic findings. This important characteristic, which has been validated in a wide set of preclinical studies, forms a foundation for the use of transplanted stem cell populations as vehicles for the delivery of tumor-toxic molecules to sites of intracranial tumor [9, 14]. The significance of neuronal stem cell (NSC)-based gene therapy for brain tumor is that it is possible to exploit the tumor-tropic Corresponding author: Bernhard Schaller MD, PhD, DSC University of Oradea Romania Phone: 079 666 99 42b E-mail: skull_base-surgery@yahoo.de Editorial