By Patrick Yang ’20

With average survival for glioblastoma patients at approximately 12-15 months, speed is of essence for glioblastoma cancer treatment. Currently, promising stem cell research has found that neural stem cells naturally migrate towards the chemical signals released by glioblastoma cells. If these neural stem cells are engineered to contain cytotoxic agents, they can deliver cancer treatment directly to cancer cells. However, the process to revert human cells to an undifferentiated state and then convert them into neural stem cells, also known as transdifferentiation, is a lengthy process that can take weeks. In addition, cells from another human cannot be transdifferentiated preemptively because of potential autoimmune responses in the recipient. An effective treatment for aggressive cancers, such as glioblastoma, would need to transdifferentiate the patient’s own cells into cytotoxic neural stem cells in a short amount of time.

In a recent study led by Dr. Shawn D. Hingtgen of the University of North Carolina, a method was developed to quickly transdifferentiate human skin cells into ideal drug carriers. The process involved reverting human skin cells to a basic and undifferentiated state with SOX2 transcription factor and then culturing them in neural stem cell-inducing medium. Over the course of 48 hours, the cells formed neurospheres, or clusters of neural stem cells, and began to create nestin, an indicator of neural stem cells. To employ the tumor-homing capabilities of these newly created neural stem cells, the stem cells were engineered to express a proapoptotic molecule, or drug, to create a drug-delivering stem cell called h-iNSCTE–sTR.

To test h-iNSCTE–sTR, researchers implanted human glioblastoma cells into the brains of mice. Then, they treated the mice with either h-iNSCTE–sTR or neural stem cells without the drug. Volume of the tumor was gauged through bioluminescence. By day three, h-iNSCTE–sTR treatment had inhibited tumor growth. The h-iNSCTE–sTR treated mice had tumors that were 50-fold smaller than control animals, therefore prolonging their survival to 50 days, as opposed to 25 days.

The ability to produce drug-delivering stem cells that effectively double survival time in a short amount of time is a large step towards a practical treatment for humans. Because this research used human glioblastoma cells in their murine models, this treatment is especially promising in a clinical setting. With such a short preparation time, these tumor-homing neural stem cells will be able to treat aggressive tumors in a practical time frame.

References:

1. Juli R. Bagó, et al., Tumor-homing cytotoxic human induced neural stem cells for cancer therapy. Science Translational Medicine 9, (2017). doi: 10.1126/scitranslmed.aah6510.
2. Image retrieved from: https://commons.wikimedia.org/wiki/File:Glioblastoma_-_MR_sagittal_with_contrast.jpg