Human fat may be a Trojan horse in the fight against brain cancer

Stem cells derived from human body fat have been successfully used to deliver biologic treatments directly to the brains of mice with the most common and aggressive form of brain tumor, significantly extending their lives.

The experiments advance the possibility that the technique could work in people after surgical removal of brain cancers called glioblastomas to find and destroy any remaining cancer cells in difficult-to-reach areas of the brain. Glioblastoma cells are particularly nimble; they are able to migrate across the entire brain, hide out, and establish new tumors. Cure rates for the tumor are notoriously low as a result.

In mouse experiments, the investigators from Johns Hopkins Medicine in Baltimore, Maryland, used mesenchymal stem cells (MSCs), which have an unexplained ability to seek out cancer and other damaged cells. The MSCs had been harvested from human fat tissue and modified to secrete bone morphogenetic protein 4 (BMP4). BMP4 is a small protein that regulates embryonic development and has some tumor suppression function. The researchers, who had already given glioblastoma cells to a group of mice several weeks earlier, injected stem cells armed with BMP4 into their brains.

In a report published in Clinical Cancer Research (2014; doi:10.1158/1078-0432.CCR-13-1415), the investigators say the mice treated this way had less tumor growth and spread, and their cancers were overall less aggressive and had fewer migratory cancer cells compared to mice that did not get the treatment. Meanwhile, the mice that received stem cells with BMP4 survived significantly longer, living an average of 76 days, as compared to 52 days in the untreated mice.

"These modified mesenchymal stem cells are like a Trojan horse, in that they successfully make it to the tumor without being detected and then release their therapeutic contents to attack the cancer cells," said study leader Alfredo Quinones-Hinojosa, MD, of Johns Hopkins.

Standard treatments for glioblastoma include chemotherapy, radiation, and surgery, but even a combination of all three rarely leads to more than 18 months of survival after diagnosis. Finding a way to get biologic therapy to mop up what other treatments cannot get is a long-sought goal, said Quinones-Hinojosa. He cautioned that years of additional studies are needed before human trials of fat-derived MSC therapies could begin.

Quinones-Hinojosa, who treats patients with brain cancer at Johns Hopkins Kimmel Cancer Center, said his team was heartened by the fact that the stem cells let loose into the brain in his experiments did not transform themselves into new tumors.

Ideally, if MSCs work, a patient with a glioblastoma would have some adipose tissue (fat) removed from any number of locations in the body a short time before surgery. The MSCs in the fat would be drawn out and manipulated in the lab to secrete BMP4. Then, after removing the brain tumor, the surgeon could deposit these treatment-armed cells into the brain in the hopes that they would seek out and destroy the cancer cells.

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