So how could this new cell elude scientists and doctors for so long? Somehow, it never happened. Plikus and his graduate student sifted through centuries of scientific papers for any missing trace of fatty cartilage. They found a clue in an 1854 German book by Franz Leydig, a contemporary of Charles Darwin. “Anything and everything he could stick under a microscope, he did,” Plikus said. Leydig’s book described fat-like cells in a sample of cartilage from the ears of mice. But the tools of the 19th century could not extend beyond that observation, and, realizing that a more accurate census of bone tissue might be useful in medicine, Plikus decided to break the case.
His team began their investigation by looking at the cartilage between the thin layers of skin in a mouse’s ear. A green dye that stains the fat molecules reveals a network of squishy blobs. They isolated these lipid-laden cells and analyzed their contents. All of your cells contain the same library of genes, but those genes don’t always work. What genes were expressed by these cells? What proteins go inside? That data revealed that lipochondrocytes actually look very different, molecularly, from fat cells.
They next asked how lipochondrocytes behave. Fat cells have a mysterious function in the body: to store energy. When your body stores energy, the cellular stores of lipids swell; when your body burns fat, cells shrink. Lipochondrocytes, it turns out, do no such thing. Researchers studied the ears of mice fed a high-fat diet compared to calories. Despite rapid growth or weight loss, the lipochondrocytes in the ears did not change.
“That immediately suggested that they must have a completely different role that has nothing to do with metabolism,” Plikus said. “There has to be structure.”
Lipochondrocytes are like balloons filled with vegetable oil. They are soft and amorphous but still resistant to compression. This has a noticeable effect on the structural properties of cartilage. Based on data from mice, the tensile strength, stiffness, and stiffness of cartilage increased by 77 to 360 percent when compared with cartilage tissue with and without lipochondrocytes—suggesting that these cells make cartilage flexible.
And structural gifts seem to benefit all species. For example, in the outer ear of Pallas’s long-tongued bat, the lipocartilage lies beneath a series of ridges that scientists believe correlate with the precise pitch of sound.
The team found lipochondrocytes in human fetal cartilage, too. And Lee says the findings seem to finally explain something reconstructive surgeons often see: “Cartilage is always a little slippery,” he said, especially in young children. “You hear it, you see it. It’s very obvious.”
New findings suggest that lipochondrocytes fine-tune the biomechanics of some of our cartilage. The solid cartilage protein scaffold without lipids is durable and is used to build weight-bearing joints in your neck, back, and—yes, you got it—ribs, one of the traditional sources of artificial cartilage. “But when it comes to very complex things that need to be soft, strong, stretchy—the ears, the nose, the throat,” Plikus says, that’s where lipocartilage shines.
Through processes that involve modifying these organs, Plikus envisions one day growing lipocartilage organoids in a container and 3D printing them into any desired shape. However, Lee urges: “Despite 30 or 40 years of study, we cannot make complex tissues,” he said.
Although surgery like this is a long way off, research suggests it may be possible to grow lipochondrocytes from embryonic stem cells and safely isolate them for transplantation. Lee notes that regulators would not green light using embryonic cells to grow tissue for a non-life-threatening condition, but says he would be optimistic if researchers could grow transplantable tissue from adult cells obtained from a patient. (Plikus says the new patent application covers the use of stem cells from the tissues of adults.)
Lipochondrocytes advance our understanding of how cartilage should look and feel—and why. “When we try to build, say, the nose, sometimes we can use it [lipid-filled cells] for a little padding.” Lee says. Lipocartilage could one day fill that space as a pliable, graftable tissue—or it could promote better biomimicking. It could be both. “It’s interesting to think about. Maybe that’s one thing we’ve been missing,” Lee says. .”