Brain Tissue Model Devised for Cancer Drug Testing

Mini-brain spheroid model (MicroMatrices Associates)

6 Feb. 2019. A three-dimensional brain tissue model, including a patient’s tumor cells, shows in lab tests an ability to test current and experimental cancer drugs. A team from the company MicroMatrices Associates Ltd. in Dundee, Scotland, U.K. as well as academic researchers describe the device and tests in yesterday’s issue of the journal Scientific Reports.

The researchers led by MicroMatrices founder and managing director Simon Plummer are seeking faster, more reliable, and personalized methods for testing prospective treatments for glioblastoma and other cancers in the brain. Most preclinical drug research uses animals for both safety and efficacy testing, which according to the authors is hampered by a low correlation between animal and human physiology. In this study, the researchers assess a human brain tissue model that takes advantage of advances in stem cells and microfluidics, or lab-on-a-chip, technologies as a substitute for animal testing.

The MicroMatrices system uses collections of cells formed into spheroid micro tissue arrays that the company calls SpheroMatrices. These collections contain different types of cells, including in this case neurons or nerve cells from the brain, with supporting glial and astrocyte cells called BrainSpheres. Cells in the model are derived from induced pluripotent or adult stem cells, and grown into small 3-D spheres known as organoids. A recent study by many of the same authors shows BrainSpheres can be produced in large numbers and consistent quality to test drugs for toxicity to nerve cells.

Plummer and colleagues extended their BrainSphere technology to gauge the efficacy of drugs for treating glioblastoma, a form of brain cancer. Glioblastoma is an aggressive cancer that affects astrocyte or glial cells supporting neurons in the brain. The disease is often difficult to treat, where usually the best hope is to slow its progression with radiation or chemotherapy. Survival from initial tumors is typically 20 months and those with recurring glioblastoma usually survive for less than a year.

In this case, the researchers added glioblastoma tumor cells from a patient with the disease to the BrainSphere organoids. With these tools, the team tested two drugs for treating glioblastoma. Temozolomide is a current drug approved for glioblastoma, taken as a capsule after surgery to remove the tumor or radiation treatment. The authors note that in some patients, resistance to temozolomide develops that limits the drug’s effectiveness. The other drug, doxorubicin, is currently approved for some blood-related and soft-tissue cancers, but not glioblastoma. In lab tests, however, doxorubicin shows promise against glioblastoma cells.

The tests show untreated glioblastoma tumor cells in the BrainSpheres grew in size for 4 weeks on SpheroMatrices platform. When treated with temozolomide, the tumors reduced in size by about 30 percent. Treatments with doxorubicin, however, resulted in about an 80 percent reduction in tumor size. In both cases, tumor cells were killed after the exposure to the drugs, while the number of non-cancerous brain cells remained unchanged. The researchers conclude BrainSpheres and SpheroMatrices are a feasible cancer drug testing technology, not only for drug discovery, but also for testing prospective treatments with a patient’s own tumor cells.

Among the paper’s authors are Thomas Hartung, a professor of environmental health and engineering at the Johns Hopkins University school of public health in Baltimore and David Pamies, a postdoctoral researcher at Johns Hopkins. Hartung and Pamies are listed as inventors on a patent for mini-brain organoids, and Hartung founded the company Organome LLC in Baltimore to commercialize the technology.

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