In 2014, Fine read the paper that launched the brain organoid revolution. It explained how biologists had coaxed human stem cells to develop into uncannily realistic miniatures of human brains.
“That’s what we need,” Fine recalls thinking. He called the authors and got more details about their organoid recipe. “We putzed around and tried different things,” he said, and after some false starts — they weren’t using quite the right brain-making ingredients, so the stem cells developed into micro-pancreases and colons — it worked.
“Within six weeks, we now have a brain organoid” with three of the six cortical layers that full-grown human brains have, he said. They even birthed specialized neurons that crackle with electrical activity and form circuits.
Now he and his team are putting cells from human brain tumors into the organoids, which have reached the level of development and complexity of a 20-week-old human fetus’, to see whether they reprise what happens in patients.
According to his unpublished findings, when he puts glioblastoma cells from patients into lab dishes with brain organoids, the cells attach to the surface of the organoids, burrow into them, and within 24 to 48 hours grow into a mass that eventually “looks exactly like what happened in the patient’s own brain,” Fine said.
For one thing, the mini-tumors sprout microtubes that connect individual tumor cells and seem to underlie glioblastomas’ resistance to chemotherapy and radiation. For another, the tumors in the brain organoids “mimic how far and how fast” the patient’s own cancer grew, “and how destructive it was,” Fine said. “The tumor stem cells kill the organoid in two weeks.”
His team’s first brain organoids were created from the cells of healthy people. But now they are making them from brain cells of glioblastoma patients. “We need to get the [tumor] stem cells to grow in an environment much more like a patient’s brain,” he said. What could be more “like” a patient’s own brain than a miniature one grown from her own cells, and therefore containing DNA identical to hers?