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In the last five years, researchers have engineered lots of dish-dwelling micro-organs, from itsy bitsy intestines to Lilliputian livers. They’ve simultaneously made major advances in biochips: small, Flash-drive-sized structures lined with a layer or two of cells and studded with biosensors and microfluidic channels. Those two-dimensional chips are useful for testing, say, how lung cells react to a piped-in toxin, but they’re too simplistic to truly mimic organs. That’s where organoids like Hoffman-Kim’s brain balls come in. For the first time, 2-D biochips are colliding with 3-D mini-organs—and together they’re making some of the best organ simulations ever.
Using these mashups, the idea is that scientists will be able to take a few of your skin cells, grow miniature versions of all your major organs, and put them on a chip. Then doctors can test out the best compounds for whatever disease you might have—not in a mouse, but in a mini-you. “This will enable a new era of personalized medicine,” says Ali Khademhosseini, a bioengineer at Harvard’s Wyss Institute who has been working on both mini-organs and biochips for the last decade.
This new kind of drug-testing system could make it faster and cheaper to develop new therapeutics. Darpa has been a big funder of this line of research, especially as it aims at treatments for nuclear or biological weapons that are difficult to test in humans. And it could mean the end of animal test subjects; currently, all new drugs must be tested for toxicity on animals before the developer can apply for a human trial. That’s especially great news for diseases that only hit humans, where animal models aren’t that useful in the first place.
Take enteroviruses. Each year they cause over 10 million nasty infections—they’re particularly deadly for newborns—but none of their 71 strains naturally infect mice or rats. “If you think about it, most everything we know about infectious diseases comes from the mouse,” says Carolyn Coyne, a microbiologist at the University of Pittsburgh. So Coyne made a mini-gut instead. In a paper published last month, her team took human stem cells and nudged them to develop into the seven different cell types that make up the human gut. Just like Hoffman-Kim’s mini-brains, Coyne’s cells self-organized into blobs of proto-intestines, complete with finger-like villi. Some enteroviruses targeted certain cells and not others, using them to gain passage into the bloodstream where they cause the most damage.