Researchers used cytochalasin D, a naturally occurring substance found in mold, as a proxy to alter gene expression in the nuclei of mesenchymal stem cells to force them to become osteoblasts (bone cells).
By treating stem cells - which can become fat or bone cells - with cytochalasin D- the result was clear: the stem cells became bone cells. Further, injecting a small amount of cytochalasin D into the bone marrow space of mice caused bone to form. This research, published in the journal Stem Cells, details how the scientists altered the stem cells and triggered bone growth.
At the center of the discovery is a protein called actin, which forms fibers that span the cytoplasm of cells to create the cell's cytoskeleton. Osteoblasts have more cytoskeleton than do adipocytes (fat cells). The team used cytochalasin D to break up the actin cytoskeleton. In theory - and according to the literature - this should have destroyed the cell's ability to become bone cells. The cells, in turn, should have been more likely to turn into adipocytes. Instead, authors found that actin was trafficked into the nuclei of the stem cells, where it had the surprising effect of inducing the cells to become osteoblasts.
They also found that when actin enters and stays in the nucleus, it enhances gene expression in a way that causes the cell to become an osteoblast. The team then turned to a mouse model. Using live mice, they showed that cytochalasin D induced bone formation in mice.
Bone formation in mice isn't very different from that in humans, so this research might be translatable. And while cytochalasin D might not be the actual agent scientists use to trigger bone formation in the clinic, the study shows that triggering actin transport into the nuclei of cells may be a good way to force mesenchymal stem cells to become bone cells.