Human skeletal stem cells can form new bone and cartilage.
Chan and Longaker et al., Cell 175, 1 (2018)
Researchers have finally triumphed in a decadeslong quest to identify human stem cells that reliably develop into the bone, cartilage, and other tissues that make up the body’s skeleton. The discovery, from a team that had previously identified such cells in mice, could pave the way for new treatments for fractures, joint damage, and osteoporosis. What’s more, these cells can apparently be coaxed into existence from fat that is normally discarded after liposuction, hinting at an abundant potential reservoir of stem cells to seed future research and therapies.
The finding is a welcome confirmation that the cells exist in people, says Michael Kyba, a pediatric cancer researcher who studies stem cells at the University of Minnesota in Minneapolis who wasn’t involved in the research. “Humans are a much more complex system than mice … so it’s important.”
Early hunting expeditions for skeletal stem cells in human bone uncovered so-called mesenchymal stem cells. These mixtures of different kinds of stem cells can become skeletal tissue like bone and cartilage, but also fat, muscle, connective tissue, and blood vessels. Researchers struggled to pin down the precise cells that give rise to the new skeletal tissue.
In 2015, a team led by Michael Longaker of Stanford University in Palo Alto, California—he describes himself as “a stem cell biologist trapped in a plastic surgeon’s body”—and his colleague, plastic and reconstructive surgeon Charles Chan, looked at the mesenchymal stem cells inside “rainbow mice.” This rodent strain has been genetically engineered so that different stem cell types have distinct colors, allowing researchers to track exactly which ones give rise to skeleton-forming cells. Then, the team identified the genes in those cells, revealing a genetic signature for skeletal stem cells in mice.
Repeating the process in our own species proved less straightforward, says Longaker, “because we don’t have ‘rainbow humans.’” Instead, he and colleagues worked with human fetal bones obtained from a company that provides tissues from fetuses that were aborted or otherwise did not survive. In these, they looked for cells sporting a similar genetic signature to the mice stem cells in the growth plate, the region of bone where new growth occurs during development. From those cells, the researchers isolated cells that could reliably form new bone and cartilage in lab dishes.
To confirm they really had skeletal stem cells, the team obtained adult human bone fragments, which had been freshly cut out during hip and knee replacement surgery. They located the signature cells and grew them in dishes. Once again the cells formed new bone and cartilage, the researchers report today in Cell. Importantly, the cells didn’t turn into fat, muscle, or anything else. “These are true skeletal stem cells,” Longaker says.
To find a way to reliably produce a large number of such cells, the team cultured some genetically modified normal adult cells, called induced pluripotent stem cells, in a bath of bone growth–promoting compounds and vitamins. When isolated and grown in a dish, these cells, too, only developed into bone and cartilage.
The study identified one further, and unexpected, potential source skeletal stem cells: liposuctioned fat. Certain cells called stromal cells within fatty blood vessels are actually a type of stem cell. By isolating those cells and growing them in a dish alongside a bone growth factor protein, the scientists created skeletal stem cells.
“A half-million times a year, U.S. citizens have their fat sucked out and it’s discarded as medical waste,” Longaker said. “That’s a lot of material we could use to generate skeletal stem cells.” Though practical applications are still years away, he envisions these cells being used to replace damaged bone and joint tissue or treat degenerative skeletal diseases like osteoporosis.
“This is a major step forward,” says John Adams, a molecular biologist and physician at the David Geffen School of Medicine at the University of California, Los Angeles. But he says the researchers still need to prove they can scale up the production of these cells. “Whether they can isolate them in large enough quantities to be clinically useful, that’s going to take a while to find out.”