Researchers at the University of North Carolina (UNC) School of Medicine are on to something significant. They have found a way to get mesenchymal stem cells to become not the customary fat cells but osteoblasts—bone cells. The researchers used cytochalasin D, a naturally occurring substance found in mold, to alter gene expression in the nuclei of mesenchymal stem cells. To the researcher’s astonishment, this forced them to become bone cells.
Researchers Turn Mesenchymal Stem Cells Into Osteoblasts
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“This was not what we expected. This was not what we were trying to do in the lab. But what we’ve found could become an amazing way to jump-start local bone formation, ” said Janet Rubin, M.D., senior author of the paper and professor of medicine at the UNC School of Medicine. She added, “And the bone forms quickly. 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.” By injecting a small amount of cytochalasin D into the bone marrow of mice the researchers had caused bone to form.
As reported by the journal BioScience Technology the protein called actin, forms fibers that span the cytoplasm of cells to create the cell’s cytoskeleton. Osteoblasts have more cytoskeleton than do adipocytes (fat cells). Buer Sen, M.D., first author of the research published in the journal Stem Cells and research associate in Rubin’s lab, used cytochalasin D to break up the actin cytoskeleton. This should have destroyed the cell’s ability to become bone cells, he noted. Instead, Sen 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.
Rubin’s first reaction to Sen’s discovery was disbelief. “This must be wrong. It goes against everything in the literature.” Sen replied, “I’ve rerun the experiments. This is what happens.”
Rubin’s team expanded the experiments and 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.
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This is a fascinating development. In my practice we've seen similar outcomes with the revised protocol. The key differentiator seems to be patient selection criteria. Has anyone else noticed the correlation with BMI thresholds?
Great point. I'd push back slightly on the conclusion, the sample size in the cited study is too small to draw population-level inferences. That said, the directional signal is compelling and worth a larger RCT.
We implemented a similar approach last year. Early results are promising but we're still gathering 12-month follow-up data. Happy to share our protocol if anyone is interested.
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