Bioengineers Program Cells to Fold Into 3D Shapes

California researchers engineered cells from mice and humans to fold, coil, and ripple, which could advance efforts to grow tissue and organs.

Scientists have replicated some of the processes that cause cells to fold, coil, and ripple as they become flesh. Publishing their findings recently in the journal Developmental Cell, researchers at University of California campuses in Berkeley and San Francisco said their discovery was a major leap in growing tissues and organs and developing new medical therapies in the future.

“I’m really interested in self-organization and how cells self-organize into tissues and organs,” Zev Gartner of the university’s Center for Cellular Construction and a senior author on the journal article told Seeker. “If we want to build with biology, that’s the engineering language we need to learn.”

The key to Gartner and his colleagues’ discovery were mesenchymal stem cells, which he said bind other cells to one another in the same way mortar holds together bricks. They studied the cells in mouse digestive tracts, observing how the cells pushed and pulled collagen — the most prevalent type of protein in the animals — into shapes that eventually would become villi, or small projections in the intestines that help absorb nutrients.

In the lab, they placed mesenchymal cells from mice and humans on collagen fibers that were as long as a centimeter, then watched as the fibers warped into different shapes. “It happens over a couple hours. It’s pretty fast,” he said. “I was totally blown away.”

They also figured out how to predict the shapes that the cells would create based on their placement on the collagen and other factors, making fruit rollup-like wraps, tubes, and abstract designs like the Miura fold, a popular origami design.

They also placed other cells, like endothelial cells from human umbilical veins, on the collagen and found that they would fold up, too, and in certain circumstances help construct new shapes.

Lastly, they purposely introduced errors and challenges to prevent the mesenchymal cells from folding the collagen. But often the cells continued to fold, suggesting they were robust enough for further engineering in the future.

Gartner envisioned someday stringing cells together to make organs and other tissues.

“A single mesenchymal cell can sort of change the architecture of the collagen around it,” he said. “But large networks of these cell that link up spatially, hundreds of thousands of these cells working together, arranged in certain ways, can now do really incredible things, folding up these tissues into really elaborate and beautiful patterns.”

Crafting new organs opens the door to transplants, personalized medicine, testing cures for diseases, and researching how and why tissues grow incorrectly. To achieve commensurate test tissues, current technology demands that researchers clone an organism, then harvest the clone’s organs — an ethically questionable approach. Three-dimensional printing can also produce versions of organs, but they usually can’t yet be called duplicates of their organically grown counterparts.

“There is going to have to be some sort of engineering of these tissues, whether in other organisms or bioreactors we make in a dish,” said Gartner. “In order to do that, we are going to have to understand how development works.”

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