So how did this new cell escape the eyes of scientists and doctors for so long? In a way, it didn't. Plikus and his graduate students scoured scientific papers over the centuries to find any trace of lost 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 a microscope, he did,” Plikus said. Leydig's book describes fat-like cells in cartilage samples from mouse ears. But the tools of the 19th century could not extend beyond that observation, and realizing that a more accurate census of bone tissue could be valuable to medicine, Plikus determined to solve the case.
His team began their investigation by looking at the cartilage located between the thin layers of mouse ear skin. A green dye preferentially stains fat molecules to reveal a network of pasty blobs. They isolated these lipid-filled cells and analyzed their contents. All of your cells contain the same library of genes, but those genes aren't always turned on. What genes did these cells express? What proteins are inside? That data revealed that lipochondrocytes actually look molecularly very different from fat cells.
Next they asked questions about how lipochondrocytes work. Fat cells have an unmistakable function in the body: energy storage. As your body stores energy, the amount of lipid stored in your cells increases; When your body burns fat, cells shrink. Turns out, lipochondrocytes don't do that. Researchers studied the ears of mice on a high-fat, calorie-restricted diet. Despite rapid weight gain or loss, the lipochondrocytes in the ear remain unchanged.
“That immediately suggests that they must have a completely different role, which has nothing to do with metabolism,” Plikus said. “It has to have structure.”
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 data from rodents, the tensile strength, resilience and stiffness of cartilage increased by 77 to 360% when comparing cartilage tissue with and without lipochondrocytes – suggesting that these cells make Cartilage is more flexible.
And the structural gifts seem to benefit all species. For example, in the outer ear of Pallas's long-tongued bat, fatty cartilage lies beneath a series of wrinkles that scientists believe can tune them to precise sound wavelengths.
The research team also discovered lipochondrocytes in human fetal cartilage. And Lee said the finding seems to finally explain something reconstructive surgeons often observe: “Cartilage is always a little slippery,” she said, especially in young children. “You can feel it, you can see it. That's very clear.”
New findings show that lipochondrocytes fine-tune the biology of some of our cartilage. A rigid framework 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—the ribs, one of the traditional sources of cartilage for implants . “But when it comes to more complicated things that really need to be pliable, bouncy, elastic like the ears, the tip of the nose, the larynx,” Plikus says, that's where fatty cartilage shines.
As for procedures that involve modifying these parts of the body, Plikus one day envisions growing lipoprotein cartilage organoids in a dish and 3D printing them in any shape. any wish. Still, Lee urges caution: “Despite 30 or 40 years of research, we are still not good at creating complex tissues,” she says.
Although such an operation is still far off, research shows that growing lipochondrocytes from embryonic stem cells and safely isolating them for transplantation is feasible. Lee expects that regulators will not green-light the use of embryonic cells to grow tissue for non-life-threatening conditions, but said she will be more optimistic if researchers can develop grow transplantable tissue from patient-derived adult cells. (Plikus said in a new patent application that he applied for the application using stem cells from adult tissue.)
Lipochondrocytes update our understanding of what cartilage looks and feels like—and why. “When we're trying to build a nose, for example, sometimes we can use (lipid-filled cells) to cushion it a little bit.” Lee said. Lipocartilage could one day fill that gap as a growable and implantable tissue – or it could inspire better biomimetic materials. “It could be both,” she said. “It's interesting to think about that. Maybe that was something we missed.”