Scientists have long grown cells in flat dishes, which is handy if you're studying flat tissues. But organs have bulges and ridges and other shapes, and growing cells to mimic that geometry has been a challenge. Now, researchers have come up with a simple way to raise cells in tall, thin columns that better re-create the natural structure of the human intestine.
It should prove useful in lab studies and perhaps someday in people without enough intestine of their own, says Dr. Daniel Teitelbaum, a gastrointestinal surgeon at the University of Michigan Medical School in Ann Arbor, who was not involved in the study.
The intestine isn't just a smooth tube: Finger-like projections called villi make the interior of the organ look more like a lush, grassy lawn. These projections give the intestine more surface area to absorb nutrients from food.
Growing cells in a flat dish misses out on many features of this 3-D system, says study author John March, an assistant professor of biological and environmental engineering at Cornell University in Ithaca, N.Y. It's like trying to understand high-rise apartment living by examining suburban bungalows — you'd learn a few things, but you'd miss out on a lot too.
For example, in the real three-dimensional intestine, the amounts of oxygen, bacteria and secretions vary from the tops of the villi to their crowded-together bottoms, says William Bentley, a bioengineer at the University of Maryland in College Park who was not involved in the study. That affects how the organ works and how nutrients are absorbed.
Scientists are working on all kinds of methods to grow cells in 3-D, but until now, the best artificial intestines have come out looking kind of "dome-y," March says, instead of tall and thin. He and his lab mates solved the problem by growing the cells, high-rise-style, on a soft gel scaffold made of collagen, one of the body's natural structural materials.
They created the villus-like pillars they wanted from a series of molds.
They started by lasering away villus-like cavities in a piece of plastic, then using that as a mold for a silicone version.
The silicone creation "looks like a piece of plastic, and it feels like it's got a really fine brush," March says. "It feels like the inside of an intestine."
Next, they used the silicone to create a negative mold made of alginate, a natural gel from algae. Then they molded their final collagen scaffold into the alginate — and gently dissolved away the alginate, leaving the delicate collagen scaffold intact.
Finally, the scientists planted intestinal cells on top of the collagen. As the cells grew, they ate away the collagen, taking its place and forming tall peaks that look remarkably like villi.
"These shapes fairly accurately replicate the dimensions and the three-dimensional nature of the gastrointestinal tract," Teitelbaum says.
March plans to use the artificial intestines to study how bacteria interact with the cells of the intestine. He also hopes to add more kinds of cells to better approximate the many layers of a real intestine.
The technique could be useful in making any other tall, thin biological structures, such as certain types of muscles. Perhaps, Bentley suggests, researchers could use a similar approach to make an artificial tongue with taste buds sticking up.
And although it's far too early to start putting artificial intestines in people, Teitelbaum sees promise here. Some babies are born without enough intestine; other people lose sections to cancer or Crohn's disease. Perhaps someday this technology could lead to artificial replacements.