Making Human Organs on a Chip

Harvard's Wyss Institute has developed chips to simulate organs, including a lung, pictured Wyss Institute

Disembodied human organs floating in jars are a staple of any cinematically correct mad-scientist laboratory. Researchers at Harvard’s Wyss Institute have done one better. They’ve created an organ on a chip: a device the size of a thumb drive (or, for that matter, a thumb), containing living cells, that mimics the behavior of a human organ.

The researchers have created a lung on a chip, as well as an intestine, a kidney, and bone marrow. A heart is in the works. Devices like these could radically streamline the drug testing process—currently expensive, inefficient, and lethal for many animals—and shed light on how diseases develop.

The organs on chips that the Wyss researchers have produced look a lot more like chips than organs. They’re transparent plastic rectangles with tiny channels running through them, connected to tubes and wires. “It’s the minimal physically functional section of an organ,” says Dr. Donald Ingber, who runs the institute and works with the researchers creating the various devices.

The lung on a chip has a channel running down its center with a porous membrane bisecting it lengthwise. On one side of the membrane is a layer of human capillary cells, with a blood-like fluid running along them; on the other side a layer of human air sac cells, with air running along them. Just as in a lung, the interaction of the two types of cells pulls oxygen from the air and fixes it in blood. The flexible plastic of the chip expands and contracts as the lung “breathes.”

The creation of the chips was enabled by advances in the semiconductor industry that allowed for precision manufacturing at cellular scales. But they also grew out of the increasing appreciation among biologists of the role that mechanical factors play in how the body develops and works. Ingber himself did much of the research that illustrated the point, showing, for example, that simply squeezing certain cells in a developing mouse embryo leads them to begin to differentiate into organs.

The gut on a chip that the Wyss researchers developed illustrates the point in its own way. The tiny artificial organ mimics peristalsis, the rippling contractions of the human digestive system. In so doing it surprised its creators by causing the intestinal cells lining the chip to spontaneously form the distinctive villi structure they assume in actual human intestinal walls.

The organs on chips can’t actually do all the things real organs do. Among other things, they don’t have nerve cells, and you wouldn’t want to try to digest a hot dog with the gut on a chip. But in other ways they seem to replicate the performance of actual organs very well. When the finicky microbes that live in an actual human intestine—and perform vital functions there—are introduced into the gut on a chip, they find the environment quite congenial. And the researchers who designed the lung on a chip discovered they were able to use it to predict how the lungs in living, breathing animals absorbed the particulate matter in air pollution.

The Wyss Institute is already working with a few pharmaceutical companies to design drug tests that use the organs on chips. Animal tests, after all, are expensive, increasingly controversial, and often don’t predict how humans will react to a compound. According to Ingber, the chips will also allow researchers to observe the mechanism of both diseases and drugs.

“Sometimes you might think your drug works this way. You give it for a month, kill the animal, then do a histological study,” Ingber says. That means you have to infer the mechanism after the fact. The chips, on the other hand, would allow researchers to watch the process in real time. Once they’re perfected, they can be cheaply made, and tests run repeatedly at little cost.

And once enough organs on chips have been developed, Ingber envisions creating an entire human body on chips. A pharmaceutical company could test a drug on the whole body, or on a particular subset of organs, by just plugging them together like strings of Christmas lights.

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