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So how could this new cell elude scientists and doctors for so long? In a way, it wasn’t. Plikus and his graduate student have scoured centuries of scientific papers for any lost 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 put under the microscope, he did,” says Plikus. Leydig’s book described fat cells in a sample of cartilage from rat ears. But the tools of the 19th century could not expand beyond that observation, and, realizing that a more accurate census of skeletal tissue could be valuable for medicine, Plikus resolved to crack the case.
His team began their investigation by looking at the cartilage found between thin layers of mouse ear skin. A green dye that preferentially stains fat molecules revealed a network of squishy blobs. They isolated these lipid-filled cells and analyzed their contents. All of your cells contain the same library of genes, but those genes are not always turned on. What genes do these cells express? What proteins slush around inside? That data revealed that lipochondrocytes actually looked very different, molecularly, from fat cells.
They then asked how the lipochondrocytes behaved. Fat cells have an unmistakable function in the body: storing energy. As your body stores energy, cellular stores of lipids expand; when your body burns fat, the cells shrink. Lipochondrocytes, it turns out, don’t do that. The researchers studied the ears of mice put on a high-fat diet versus a calorie-restricted diet. Despite the rapid weight gain or loss, the lipochondrocytes in the ears have not changed.
“This immediately suggested that they must have a completely different role that has nothing to do with metabolism,” says Plikus. “It has to be structural.”
Lipochondrocytes are like balloons filled with vegetable oil. They are soft and amorphous, but still resist compression. This contributes significantly to the structural properties of cartilage. Based on rodent data, the tensile strength, resistance, and stiffness of cartilage increased from 77 to 360 percent when comparing cartilage tissue with and without lipochondrocytes, suggesting that these cells make cartilage. more flexible.
And the structural gifts seem to benefit all kinds of species. In the outer ear of Pallas’s long-tongued bat, for example, the lipocartilage is under a series of ruffles that scientists think tunes it to precise wavelengths of sound.
The team also discovered lipochondrocytes in human fetal cartilage. And Lee says this discovery seems to finally explain something that reconstructive surgeons commonly observe: “Cartilage always has some slipperiness,” he says, especially in children. “You can hear it, you can see it. It’s very obvious.”
The new findings suggest that lipochondrocytes tune the biomechanics of some of our cartilage. A rigid scaffold of lipid-free cartilage proteins is more durable and is used to build weight-bearing joints in the neck, back, and—yes, you got it—ribs, one of the traditional sources of cartilage for implants. “But when it comes to more intricate things that actually have to be flexible, bouncy, elastic — ears, the tip of the nose, the larynx,” says Plikus, that’s where lipocartilage shines.
For procedures involving the modification of these body parts, Plikus one day envisions growing lipocartilage organoids in a dish and printing them in 3D in any desired shape. Lee, however, urges caution: “Despite 30 or 40 years of study, we’re not very good at making complex fabrics,” he says.
Although such an operation is far away, the study suggests that it is feasible to grow lipochondrocytes from embryonic stem cells and isolate them safely for a transplant. Lee figures regulators won’t allow using embryonic cells to grow tissue for a non-life-threatening condition, but says she would be more optimistic if researchers can grow transplantable tissue from adult cells derived from patients. (Plikus says that a new patent application has been filed covering stem cells from adult tissues).
Lipochondrocytes are updating our understanding of how cartilage should look and feel—and why. “When we’re trying to build, for example, the nose, sometimes we can use the (lipid-filled cells) for a bit of padding.” Lee says. Lipocartilage could one day fill this void as a cultivable and transplantable tissue – or it could inspire better biomimetic materials. “It could be both,” she says. “It’s exciting to think about. Maybe that’s something we’ve been missing.”
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