Newly identified human skeletal stem cell could lead to bone regenerative therapies

The power of human bone to heal itself is limited. Its ability to repair fractures fades with age, and adult cartilage is almost impossible to renew. But after a decade of research, Stanford University scientists have identified a human skeletal stem cell that can specifically grow into bone, cartilage and the spongy stroma of the bone’s interior, paving the way to potential regenerative treatments.

The team had previously identified a similar skeletal stem cell in mice, but isolating its human counterpart wasn’t as easy as they had predicted. Previous efforts to isolate stem cells in the bone uncovered mesenchymal cells, which weren't always potent and sometimes grew into various non-bone tissues such as fat, muscle and endothelial cells.

So the Stanford team compared the gene expression of the mouse cell with human cell types found at the tips of developing bone. Then they identified markers on the human cells’ surface that could help them isolate a pure population. What they ended up with “possesses all of the hallmark qualities of true, multipotential, self-renewing, tissue-specific stem cells. They are restricted in terms of their fate potential to just skeletal tissues, which is likely to make them much more clinically useful,” said Charles Chan, the first author of the study, in a statement. The research was published in the journal Cell.

Scientists have been exploring the use of stem cells to repair bone dysfunction. A Cedars-Sinai team, for example, successfully used a matrix of collagen and bone-inducing gene to stimulate existing stem cells to heal fractured leg bones of lab animals. But the Stanford study marks the first time that skeletal stem cells have been identified in humans.

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According to the Stanford researchers, human skeletal stem cells are present in growing fetal bone, as well as near the site of healing fractures in adult bone. They can also be derived from induced pluripotent stem cells (iPSCs) and human fat stroma treated with a protein called BMP-2, which is key in the development of bone and cartilage.

Comparing the discoveries in both mouse and human skeletal cells, the team came up with a family tree of stem cells, which could enable future research focused on identifying the genetic and molecular elements that contribute to bone formation. The discovery also offers the potential for future application in the clinic—to “facilitate the development of patient-specific approaches to diagnosing and reversing diverse types of skeletal disorders,” the researchers wrote in the paper.

Michael Longaker, the study’s senior author, envisions incorporating specifically regulated skeletal stem cell to generate cartilage in a minimally invasive procedure called arthroscopy, where a tiny camera and surgical instruments are inserted into the joint to examine or treat bone damage.

“Imagine if we could turn readily available fat cells from liposuction into stem cells that could be injected into their joints to make new cartilage, or if we could stimulate the formation of new bone to repair fractures in older people,” Longaker said in the statement.