Scientists have reprogrammed skin cells to hunt and kill brain tumor cells.
Gioblastomas are aggressive brain tumors that often lead to patient death within 12–15 months. They spread cancer cells throughout the brain, making surgical removal difficult. They also emit chemicals that attract stem cells, possibly because stem cells see tumors as wounds that need to be healed.
Scientists led by Shawn Hingtgen, a stem cell biologist at the University of North Carolina in Chapel Hill, are looking to leverage this stem cell–attracting characteristic to develop cancer treatments.
It was previously known that neural stem cells, which give rise to neurons and other brain cells, can be used to find brain cancer in mice and achieve targeted delivery of cytotoxic drugs to tumors. This approach has not been pursued extensively, however, because it is difficult to access the neural stem cells.
Hingtgen’s group decided to convert skin cells directly into neural stem cells, rather than first turning them into standard stem cells. They achieved the desired one-step process using a proprietary mixture of chemicals designed to promote neural stem cell characteristics. More importantly, these neural stem cells were observed to be attracted to tumors ex vivo. They moved 500 microns in 22 hours and burrowed into lab-grown glioblastomas.
Next, the scientists engineered the neural stem cells to deliver common cancer treatments to glioblastomas in mice. Mouse tumors injected directly with the reprogrammed stem cells shrank 20- to 50-fold in 24–28 days compared with nontreated mice, and those that were treated had their survival times nearly doubled. When tumors were surgically removed and the engineered neural cells injected into the cavity left behind, the tumors formed from the remaining cells were 3.5 times smaller than those in untreated mice.
In a human brain, the neural cells would need to travel millimeters to centimeters, so the researchers have more work to do to determine if they might be applicable for the treatment of gioblastomas in humans. They are testing how far their tumor-homing cells can migrate using larger animal models. They must also determine whether neural cells developed from someone else’s skin cells will result in undesired immune responses; if that is the case, then the patient’s own skin cells may need to be used.