UNC scientists develop a new way to prod stem cells into bone

UNC's Janet Rubin

A team led by Janet Rubin at the University of North Carolina School of Medicine recently found a novel method to push stem cells into forming bone.

In the elderly population, a common feature in patients is the weakening of joints as they age. When a bone fracture occurs, healing of the bone to restore movement in the patient is required with the formation of new bone growth around the point of the fracture to strengthen it.

In their work published in the journal Stem Cells, the investigators showed that treating stem cells that usually become fat or bone cells with cytochalasin D, which is found in mold, altered gene expression and convincingly turned them into bone cells.

They also injected cytochalasin D into the bone marrow space of mice triggering further bone growth. "And the bone forms quickly," says Rubin. "The data and images are so clear; you don't have to be a bone biologist to see what cytochalasin D does in one week in a mouse."

In a serendipitous experiment done by Buer Sen, a research associate in the lab, cytochalasin D was used initially to break up the actin cytoskeleton. According to previous literature, this should prevent the cell from forming bone and instead form fat cells. However, it was observed that actin moved into the nucleus of the stem cells and forced the cell to instead become bone cells.

"My first reaction was, 'No way, Buer,'" Rubin said. "'This must be wrong. It goes against everything in the literature.' But he said, 'I've rerun the experiments. This is what happens.'"

They went on to provide convincing data that if actin enters and stays in the nucleus, gene expression programs are induced, which turns the cell into a bone cell.

After these initial in vitro experiments, they took this into a mouse model and showed the same phenomenon. This so-called stem cell differentiation may be translatable to the clinic in the future; for now they will understand whether there are other molecules involved in this mechanism regulated by actin.

- here's the release
- read the research abstract