Development of a Stem Cell Therapy for Malignant Brain Tumours

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 shows 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 tumour microsatellites and destroy these through
the use of therapeutic transgenes constitute an attractive potential treatment strategy for
malignant glioma. In a series of initial studies grafted neural stem cells and bone marrowderived
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.