Researchers will use cellular imaging in an animal model of brain tumor to see whether human mesenchymal stem cells—which have been removed from patients’ bone marrow and inserted into the animal—migrate to brain tumor areas to guide surgical removal and deliver therapies directly to the tumors.
Deadly glioblastoma (brain tumors) remains stubbornly resistant to surgical and medical treatment. Recent research, though, suggests that adult neural stem cells have the potential to seek out, migrate to, and infiltrate brain tumors. The need to generate large numbers of these cells, however, coupled with ethical considerations, has led to interest in the possibility of using mesenchymal stem cells, which are derived from patients’ bone marrow. The investigators hypothesize that mesenchymal stem cells better delineate areas of tumor infiltration in the brain, and can therefore guide surgical removal of the tumor, while sparing unaffected brain tissue, and, that these stem cells also can deliver tumor-killing agents directly to tumor-containing brain areas.
To test these hypotheses, they will remove and label mesenchymal stem cells from patients’ bone marrow and insert the cells into an animal model of brain tumor. The cells will be labeled with particles that are both magnetic and fluorescent. This will facilitate MRI imaging in the anesthetized animals to monitor the stem cells’ distribution in the brain, and, through cellular fluorescence imaging, to visualize the stem cells throughout the whole body and also in post-mortem animal tissues. If their hypotheses are correct, the imaging will reveal that the stem cells have migrated and accumulated primarily in the tumors, regardless of their size or location in the brain; moreover, any of the stem cells that migrated to other parts of the body will have been cleared away by the body. In addition, they will fluorescently label a tumor-killing virus, which is harmless to humans, infect the stem cells with the virus, and use imaging to determine if the virus surrounds the tumors and kills tumor cells, reducing the tumor mass.
Significance: Imaging may reveal that mesenchymal stem cells can both identify brain tumors and define their margins (boundaries) to guide surgical removal. The research also may demonstrate that these stem cells can be used to target therapies directly to the tumor, providing improved and new treatment options for patients.