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Novel Stem Cell Therapy Eliminates Brain Tumors in Mouse Model

By LabMedica International staff writers
Posted on 04 May 2015
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Image: Tagged therapeutic stem cells (green) are targeting breast cancer metastases (red) in the brain of a mouse model (Photo courtesy of Dr. Khalid Shah, Massachusetts General Hospital).
Image: Tagged therapeutic stem cells (green) are targeting breast cancer metastases (red) in the brain of a mouse model (Photo courtesy of Dr. Khalid Shah, Massachusetts General Hospital).
Cancer researchers have developed a novel stem cell therapeutic approach for treating breast cancer that has spread to the brain.

Investigators at Massachusetts General Hospital (Boston, USA) and the Harvard Stem Cell Institute (Boston, MA, USA) initially developed an in vivo imageable breast-to-brain metastasis mouse model. Using real time in vivo imaging and subsequent composite fluorescence imaging, they demonstrated in the brains of the mice widespread distribution of micro- and macro-metastasis in different stages of metastatic progression. They also showed extravasation of tumor cells and the close association of tumor cells with blood vessels in the brain thus mimicking the multi-foci metastases observed in human patients.

To treat the breast tumors that had developed in the brains of the mice the investigators created a line of genetically engineered adult stem cells. The stem cells, which were known to be naturally attracted toward tumors in the brain, were modified in two ways. The genomes of the stem cells were altered by insertion of two genes, the gene for a variant of TRAIL (TNF receptor superfamily member 10A/10B apoptosis-inducing ligand) and the gene for herpes simplex virus thymidine kinase (HSV-TK).

TRAIL is a cytokine that is produced and secreted by most normal tissue cells. It causes apoptosis primarily in tumor cells by binding to certain death receptors. Since the mid-1990s it has been used as the basis for several anti-cancer drugs. The presence of the HSV-TK gene rendered the stem cells susceptible to the effects of the antiviral drug ganciclovir.

In experiments described in the April 24, 2015, online edition of the journal Brain, the investigators injected the modified stem cells into the brains of the mice. Imaging confirmed that the stem cells traveled to multiple metastatic sites and not to tumor-free areas. TRAIL secreted by the stem cells reduced growth of the tumors. Following inhibition of tumor growth, the stem cells were destroyed by injecting the mice with ganciclovir.

"Metastatic brain tumors - often from lung, breast or skin cancers - are the most commonly observed tumors within the brain and account for about 30% of advanced breast cancer metastases," said senior author Dr. Khalid Shah, professor of radiology and neurology at Massachusetts General Hospital. "Our results are the first to provide insight into ways of targeting brain metastases with stem-cell-directed molecules that specifically induce the death of tumor cells and then eliminating the therapeutic stem cells."

Related Links:

Massachusetts General Hospital
Harvard Stem Cell Institute


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