Accident Creates Bone From Stem Cells

Credit: Hellerhoff

Bone loss and frailty greatly diminish quality of life as we get older, and learning how to regrow bone across the body is a key rejuvenation target.

Stem cells are difficult to work with

We can now produce induced pluripotent stem cells from adult tissue, but differentiating them into a specific tissue is a major challenge. We’re still working on finding the exact chemical cues that create each specific cell type, and stem cells are highly sensitive. There has been progress in many areas, but we still have a way to go.

“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”

An accidental breakthrough

The research team had initially been attempting to create fat cells from a mesenchymal stem cell population, using a substance called cytochalasin D. This is a naturally occurring molecule present in mold. Mesenchymal stem cells are multi-potent, meaning they can differentiate into a number of types, but are still limited in their scope. They predominantly replenish cartilage, bone, muscle and fat cell types. 

After applying this cytochalasin D in the hopes it would alter gene expression in these stem cells and induce transformation, they found it triggered formation of osteoblasts – cells which deal with bone formation. They even found injecting a small quantity of the molecule into bone marrow in mice was able to directly trigger bone growth. 

“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”

Actin strands are labelled green. After adding cytochalasin D, they break up and collect in the nucleus (right) Credit: UNC School of Medicine

What was going on?

Cells have a cytoskeleton which performs a range of functions from cellular transport, structure and movement. One of the molecules that makes this skeleton up is called Actin, and researchers hoped cytochalasin D would break up the actin in the cytoskeleton and lead to adipocyte (fat cell) formation. Bone cells have more cytoskeleton than fat varieties. Instead of adipocyte formation, the broken up actin moved into the nucleus where it apparently initiated transformation into an osteoblast instead. When these fibres are broken up, they recollect in the nucleus and reform as a bone cell is born. 

“Amazingly, we found that the actin forms an architecture inside the nucleus and turns on the bone-making genetic program. If we destroy the cytoskeleton but do not allow the actin to enter the nucleus, the little bits of actin just sit in the cytoplasm, and the stem cells do not become bone cells”

If actin transport into the nucleus is the key element forcing stem cells to become bone cells, then a number of molecules could potentially be used instead. The findings are admittedly on mice, as per usual, but bone formation is very similar in mammals as a whole, so there is good reason to be hopeful about results in humans. 

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