Tabatabai
Fakultäten » Medizinische Fakultät » Neurologie, Klinik für » Dr. Ghazaleh Tabatabai » Tabatabai
Completed research project
| Title / Titel | Cell-based gene therapy of experimental gliomas | ||||||||
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| Abstract (PDF, 14 KB) | |||||||||
| Summary / Zusammenfassung | Glioblastomas are the most common and most malignant primary brain tumors with a very poor prognosis despite surgical resection, radiotherapy and recent advances in pharmacotherapy. Typical features of glioblastoma cells include an invasive phenotype leading to deep infiltration of the adjacent normal brain parenchyma. Accordingly, there is an urgent need for novel tumor-selective treatments that specifically target migratory glioma cells We have focused on the characterization of murine bone marrow-derived lineage-depleted (lin-) stem cell antigen-1 (Sca-1)+ Kit+ (LSK) and human peripherally mobilized CD34+ hematopoietic progenitor cells as suitable glioma-selective cellular vehicles in preclinical glioma models. Intracerebral gliomas attract bone marrow-derived hematopoietic progenitor cells (HPC) in vivo. Thus, HPC might enable the cell-based delivery of therapeutic molecules to malignant gliomas. We have characterized molecular mechanisms mediating the glioma tropism of adult hematopoietic progenitor cells (HPC). Our current focus is on optimizing imaging tools for tracking the glioma-mediated attraction of HPC in syngeneic mouse models using two-photon laser scanning microscopy, magnetic resonance imaging (MRI) and positron emission tomography. We plan to use ex vivo lentivirally transduced HPC for delivering therapeutic molecules to malignant gliomas in vivo. | ||||||||
| Publications / Publikationen | Tabatabai G, Bähr O, Möhle R, Eyüpoglu IY, Böhmler AM, Wischhusen J, Rieger J, Blümcke I, Weller M, Wick W Lessons from the bone marrow: how malignant glioma cells attract adult hematopoietic progenitor cells. Brain 2005;128:2200-2211Tabatabai G, Frank B, Möhler R, Weller M, Wick W Irradiation and hypoxia promote homing of hematopoietic progenitor cells towards gliomas by TGF-beta-dependent HIF-1 alpha-mediated induction of CXCL12. Brain 2006;129:2426-2435Tabatabai G, Herrmann C, von Kürthy G, Mittelbronn M, Grau S, Frank B, Möhle R, Weller M, Wick W VEGF-dependent induction of CD62E on endothelial cells mediates glioma tropism of adult hematopoietic progenitor cells. Brain 2008;131:2579-2595Tabatabai G, Hasenbach K, Herrmann C, Maurer G, Möhle R, Marini P, Grez M, Wick W, Weller M. Glioma tropism of lentivirally transduced hematopoietic progenitor cells. Int J Oncol 2010, in press |
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| Keywords / Suchbegriffe | malignant glioma, cell-based therapy, bone marrow-derived hematopoietic progenitor cells, lentiviral transduction, two photon laser scanning microscopy, positron emission tomography | ||||||||
| Project leadership and contacts / Projektleitung und Kontakte |
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| Funding source(s) / Unterstützt durch |
Others DFG, Koetser Foundation |
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| In collaboration with / In Zusammenarbeit mit |
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| Duration of Project / Projektdauer | Jul 2007 to Dec 2010 |