So how could this new cell have eluded scientists and doctors for so long? In a way it isn’t. Plikus and his graduate student searched through centuries of scientific papers in search of the lost trace of adipose cartilage. They found the clue in a German book from 1854 by Franz Leydig, a contemporary of Charles Darwin. “Everything he could put under the microscope, he did,” says Plikus. Leydig’s book describes fat-like cells in a sample of cartilage from rat ears. But the tools of the 19th century could not extend beyond that observation and, realizing that a more accurate inventory of bone tissue could be valuable for medicine, Plikus decided to solve the case.
His team began their investigation by looking at the cartilage sandwiched between thin layers of skin in a mouse ear. A green dye that preferentially stains fat molecules revealed a network of squishy spots. They isolated these lipid-filled cells and analyzed their contents. All your cells contain the same library of genes, but these genes are not always activated. What genes did these cells express? What proteins accumulate inside? These data revealed that lipochondrocytes actually look very different, molecularly, than fat cells.
Then they examined how the lipochondrocytes behaved. Fat cells have an unmistakable function in the body: energy storage. When your body stores energy, cellular lipid stores increase; when your body burns fat, the cells shrink. It turns out that lipochondrocytes do no such thing. The researchers studied the ears of mice fed a high-fat diet versus a calorie-restricted diet. Despite rapid weight gain 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,” says Plikus. “It has to be structural.”
Lipochondrocytes are like balloons filled with vegetable oil. They are soft and amorphous, but still resistant to compression. This contributes significantly to the structural properties of cartilage. Based on data from rodents, the tensile strength, resistance, and stiffness of cartilage increased by 77 to 360 percent when comparing cartilage tissue with and without lipochondrocytes—suggesting that these cells make cartilage more pliable.
Structural gifts seem to favor all kinds of species. For example, in the outer ear of Pallas’s long-tongued bat, lipocartilage is beneath a series of folds that scientists believe tune them to precise wavelengths of sound.
The team also discovered lipochondrocytes in human fetal cartilage. And Lee says the discovery finally seems to explain something reconstructive surgeons tend to notice: “Cartilage is always a little slippery,” she says, especially in young children. “You can feel it, you can see it. It’s very obvious.”
New findings suggest that lipochondrocytes fine-tune the biomechanics of some of our cartilage. A rigid, lipid-free cartilage protein scaffold is more durable and is used to build weight-bearing joints in your neck, back and — yes, you guessed it — ribs, one of the traditional sources of cartilage for implants. “But when it comes to more complicated things that actually have to be flexible, bouncy, elastic – the ears, the tip of the nose, the larynx,” Plikus says, that’s where lipocartilage shines.
For procedures that involve modifying these body parts, Plikus envisions one day growing lipocartilage organoids in a dish and 3D printing them in the desired shape. Lee, however, urges caution: “Despite 30 or 40 years of study, we’re not very good at making complex tissues,” she says.
Although such surgery is a long way off, the study suggests that it is feasible to grow lipochondrocytes from embryonic stem cells and safely isolate them for transplantation. Lee thinks regulators would not give the green light to using embryonic cells to grow tissue for a non-life-threatening condition, but says she would be more optimistic if researchers could grow tissue for transplants from adult cells obtained from patients. (Plikus says he has filed a new patent application using stem cells from adult tissue.)
Lipochondrocytes are updating our understanding of how cartilage should look and feel—and why. “When we’re trying to build, say, a nose, sometimes we could use [lipid-filled cells] for a little foundation.” says Lee. Lipocartilage may one day fill that void as a tissue that can be grown and transplanted—or it may inspire better biomimetic materials. “It could be both,” she says. “It’s exciting to think about. Maybe that’s one thing we’ve been missing.”