These newly identified cells could change the face of plastic surgery

How could this new cell remain away from scientists and doctors for so long? Somehow, it didn’t happen. Plekus and his graduate student scoured centuries of scientific papers for any missing trace of adipose cartilage. They found evidence in a German book from 1854 by Franz Leydig, a contemporary of Charles Darwin. “He did anything and everything he could to put under a microscope,” Plekus says. Leydig’s book described fat-like cells in a sample of cartilage taken from the ears of mice. But the tools of the nineteenth century could not extend beyond that observation, and realizing that a more precise census of skeletal tissues might be useful to medicine, Plekus decided to solve the issue.

His team began their investigation by looking at cartilage sandwiched between thin layers of mouse ear skin. The green dye that preferentially stains lipid molecules revealed a network of spongy dots. They isolated these fat-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 flow inside? These data revealed that adipocytes actually look very different, molecularly, from fat cells.

They then wondered how adipose chondrocytes behaved. Fat cells have an unambiguous function in the body: storing energy. When your body stores energy, your cellular fat stores swell; When your body burns fat, cells shrink. It turns out that adipose chondrocytes do no such thing. The researchers studied the ears of mice that were given a high-fat diet versus a calorie-restricted diet. Although weight is gained or lost rapidly, the adipose chondrocytes in the ears remain unchanged.

“This immediately suggests that they must have a completely different role, unrelated to metabolism,” Plekus says. “It has to be structural.”

Adipose chondrocytes resemble balloons filled with vegetable oil. It is soft and amorphous but still resists pressure. This contributes significantly to the structural properties of cartilage. Based on data from rodents, the tensile strength, elasticity and stiffness of cartilage increased by 77 to 360 percent when comparing cartilage tissue with and without chondrogenic adipocytes, suggesting that these cells make cartilage more elastic.

Structural talents seem to benefit all types of species. In the outer ear of Pallas’s long-tongued bat, for example, fatty cartilage lies behind a series of ruffles that scientists believe tunes it to precise wavelengths of sound.

The team also discovered adipose chondrocytes in human fetal cartilage. This discovery finally explains something reconstructive surgeons typically notice: “The cartilage always has a little bit of slippage,” especially in young children, Lee says. “You can feel it, you can see it. It’s very clear.”

New findings suggest that chondrocyte adipocytes fine-tune the biomechanics of some of our cartilage. A rigid scaffold composed of lean cartilage proteins is more durable and is used to construct weight-bearing joints in the neck, back and ribs, and is one of the traditional sources of cartilage used in implants. “But when it comes to more complex things that actually need to be flexible, bouncy, and elastic like the ears, the tip of the nose, and the throat, that’s where the fatty cartilage shines,” Plekus says.

For procedures that involve modifying these parts of the body, Plekus envisions one day growing adipose-chondrocyte organoids in a dish and 3D printing them in any desired shape. However, Lee urges caution: “Despite 30 or 40 years of study, we are not very good at making complex tissues,” she says.

Although such a process is still a long way off, the study suggests that it is possible to grow adipose chondrocytes from embryonic stem cells and safely isolate them for transplantation. Lee believes regulators will not give the green light to use fetal cells to grow tissue for a non-life-threatening condition, but she says she would be more optimistic if researchers could grow transplantable tissue from patient-derived adult cells. (Plekus says his new patent application covers using stem cells from adult tissue.)

Chondrocyte adipocytes are updating our understanding of how and why cartilage looks and feels. “When we’re trying to build a nose, for example, we can sometimes use (fat-filled cells) for a little bit of padding.” He tells me. Adipose cartilage could one day fill this void as a viable, implantable tissue, or it could inspire better biomimetic materials. “It could be both,” she says. “It’s interesting to think about. Maybe that’s the only thing we’ve been missing.”