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Bengzon Group
 | Johan Bengzon Department of Clinical Sciences |
Main Research Topics:
Development of a Stem Cell Therapy for Malignant Brain Tumors
Malignant glioma is the most common and most aggressive type of brain tumour in adults. Because of their diffuse growth and invasiveness into the brain parenchyma complete surgical removal is impossible and the tumour show a high degree of resistance to both chemotherapy and irradiation. Effective treatment of gliomas must include the killing of tumor cells that have dispersed significant distances from the bulk of tumour. An autologous cellular vector that rapidly and effectively migrate towards tumourmicrosatellites and destroy these through the use of a therapeutic transgenes constitute an attractive potential treatment strategy for malignant glioma. In a series of initial studies grafted neural stem cells and bone marrow-derived mesenchymal stem cells have been established as promising carriers of transgenes designed to kill experimental brain tumours.
Our specific aims are: 1) To clarify the capacity of grafted adult neural stem cells and bone marrow derived mesenchymal stem cells to preferentially migrate towards malignant brain tumours. 2) To effectively inhibit tumour growth by genetic modification of grafted adult stem cells using therapeutic genes such as apoptosis promoting agents, immunostimulatory agents and oncolytic substances. 3) To study proliferation and migration of endogenous neural stem cells in humans and in experimental models of intracerebral malignancies. 4) To test the hypothesis that human malignant gliomas arise from mutated normal neural stem cells.
The new knowledge contributed by these studies will be an important first step towards a clinical application of adult human stem cells as therapy for malignant brain tumours.
The studies will shed light on the ability of transplanted neural stem cells to preferentially migrate to malignant brain tumours and also on the capacity of endogenous stem cells from the subependymal zone to proliferate, differentiate and migrate to tumor cells.
The project is intended to be a first step towards clinical application of adult stem cells for glioma patients, but the project will also bring new knowledge regarding adult human neural stem cells and the mechanisms affecting the functioning of these cells.
Group members:
Daniel Bexell, MD. PhD student, Mobil arbete: 070-6197824
Salina Gunnarsson, MSc. PhD student, Tel: 046-171273, Mobil arbete: 0704-381718
Key publications:
1. Bexell D, Gunnarsson S, Tormin A, Darabi A, Gisselsson D, Roybon L, Scheding S, Bengzon J. Bone marrow multipotent mesenchymal stroma cells act as pericyte-like migratory vehicles in experimental gliomas. Mol Ther. 2009 Jan;17(1):183-90.
2. Bexell D, Gunnarsson S, Nordqvist J, Bengzon J (2007) Characterisation of the subventricular zone neurogenic response to rat malignant brain tumours. Neuroscience 147, 824-832.
3. Hellsten J, Wennström M, Bengzon J, Mohapel P, Tingström A (2004) Electroconvulsive seizures induce endothelial cell proliferation in adult hippocampus. Biol Psychiatry 55, 420-427.
4. Bengzon J, Mohapel P, Ekdahl CT, Lindvall O (2002) Neuronal apoptosis after brief and prolonged seizures. Prog Brain Res 135, 111-119.
5. Bengzon J, Hansson SR, Hoffman BJ, Lindvall O (1999) Regulation of norepinephrine transporter and tyrosine hydroxylase mRNAs after kainic acid-induced seizures. Brain Res 842, 239-242.
6. Bengzon J, Okabe S, Lindvall O, McKay RDG (1999). Suppression of epileptogenesis by modification of N-methyl-D-aspartate receptor subunit composition. Eur J Neurosci 11, 916-922.
7. Pazman C*, Bengzon J*, Somogyi R, McKay RDG (1997). Capture of novel differentially expressed genes induced by excitatory amino acid: candidates for plasticity and injury-related molecular effectors. *equal contribution. Exp Neurol 146, 502-512.
8. Bengzon J, Kokaia Z, Elmér E, Nanobashvili A, Kokaia M, Lindvall O (1997). Apoptosis and proliferation of dentate gyrus neurons early after single and intermittent limbic seizures. Proc Natl Acad Sci USA 94, 10432-10437.
9. Kokaia Z, Bengzon J, Metsis M, Kokaia M, Persson H, Lindvall O (1993). Co-expression of neurotrophins and their receptors in CNS neurons. Proc Natl Acad Sci USA 90, 6711-6715.
10. Bengzon J and Lindvall O (1993) Transplantation in experimental epilepsy. In: Basic and clinical neuroscience, Vol 5. Ed: Lindvall O. Springer Verlag, Heidelberg, pp. 39-50.
11. Ernfors P, Bengzon J, Kokaia Z, Persson H, Lindvall O (1991) Increased levels of messenger RNAs for neurotrophic factors in the brain during kindling epileptogenesis. Neuron 7, 165-176.