Physical Address
304 North Cardinal St.
Dorchester Center, MA 02124
Physical Address
304 North Cardinal St.
Dorchester Center, MA 02124
But how did this new cell escape scientists and doctors for so long? Somehow, it didn’t. Plikus and his graduate student scoured centuries of scientific papers for any lost trace of adipose cartilage. They found a clue in an 1854 German book by Franz Leydig, a contemporary of Charles Darwin. “He did anything and everything he could stick under the microscope,” Plikus says. Leydig’s book describes fat-like cells in a sample of cartilage from the ears of rats. But the instruments of the 19th century could not go beyond this observation, and Plikus, realizing that a more accurate inventory of skeletal tissue could be of value to medicine, decided to crack the case.
His team began their research by looking at cartilage sandwiched between thin layers of mouse ear skin. Green dye, which stains more fat molecules, revealed a network of squishy blobs. They isolated these lipid-laden cells and analyzed their contents. All your cells have the same gene library, but these genes are not always activated. What genes did these cells express? What proteins are circulating inside? These data revealed that lipochondrocytes actually look molecularly very different from fat cells.
They then asked how the lipochondrocytes behaved. Fat cells have an unquestionable function in the body: to store energy. When your body stores energy, cellular stores of lipids swell; When your body burns fat, cells shrink. Lipochondrocytes, it turns out, do no such thing. The researchers examined the ears of mice placed on high-fat and calorie-restricted diets. Despite rapid weight gain or loss, the lipochondrocytes in the ears did not change.
“This immediately suggested that they have a completely different role that has nothing to do with metabolism,” Plikus says. “It has to be structured.”
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, when cartilage tissue was compared with and without lipochondrocytes, the tensile strength, elasticity, and stiffness of cartilage increased by 77 to 360 percent, indicating that these cells make cartilage more flexible.
And structural gifts benefit all types. For example, the outer ear of Pallas’s long-tongued bat has lipocartilage at the base of a series of folds that scientists believe tune them to precise sound waves.
The team also found lipochondrocytes in human fetal cartilage. And Lee says the discovery finally explains something reconstructive surgeons often observe: “There’s always some slippage in the cartilage,” he says, especially in young children. “You can feel it, you can see it. This is very clear.”
New findings suggest that lipochondrocytes fine-tune the biomechanics of some of our cartilage. A rigid scaffold made of lipid-free cartilage proteins is more 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 cartilage for implants. “But when it comes to the more complex stuff, it’s actually got to be pliable, bulging, pliable—the ears, the tip of the nose, the larynx,” Plikus says, adding that’s where lipocartilage shines.
For procedures that involve replacing these body parts, Plikus envisions one day growing lipocartilage organelles in a dish and 3D printing them in any shape. Lee urges caution, however: “Despite 30 or 40 years of training, we’re not very good at creating complex textures,” he says.
Although such an operation is far off, the research suggests that it is possible to grow lipochondrocytes from embryonic stem cells and safely isolate them for transplantation. Lee doesn’t think regulators will give the green light to using embryonic cells to grow tissue for a non-life-threatening condition, but says he would be more optimistic if researchers could grow transplantable tissue from adult cells obtained from patients. (Plikus says the new patent application covers using stem cells from adult tissue.)
Lipochondrocytes are revolutionizing our understanding of how cartilage looks and feels—and why. “When we’re trying to build a nose, for example, sometimes we can use[lipid-filled cells]to fill it out a little bit.” Lee says. Lipocartilage may one day fill this gap as a growable, transplantable tissue or inspire better biomimetic materials. “It can be both,” he says. “It’s exciting to think about. Maybe this is one of the things we lack.”