Bending and stretching stem cells directs their development

Bending and stretching stem cells can tell them what cell type to become, according to Canadian researchers.

Stem cells replicate and develop into other types of cells in the body, making them useful research tools and potential treatments for diseases of cell loss – like Alzheimer's and Type 1 diabetes. Traditionally, scientists use chemical cues to direct stem cells toward a particular cell fate, but research at McGill University in Montreal has demonstrated that mechanically manipulating stem cells also has the same effect.

'The great strength of stem cells is their ability to adapt to the body, replicate and transform themselves into other kinds of cells, whether these are brain cells, heart muscle cells, bone cells or other cell types,' said Dr Allen Ehrlicher, associate professor at McGill's Department of Bioengineering and corresponding author of the study, 'but that is also one of the biggest challenges of working with them.'

The research team were eager to improve our understanding of how mechanical stimuli guide stem cell differentiation, as their use in regenerative medicine depends on how precisely they can become their target cell type. For their research, they used mouse mesenchymal stem cell (MSCs) – which generate bone, fat and blood cells.

Using specialist microscopes, they studied the shape of the MSCs and the nuclei inside, as well as the location of Yes-associated protein (YAP). YAP is a mechanosensitive protein, meaning it relays mechanical information to the nucleus.

Publishing their research in Biophysical Journal, the team found that in MSCs with very round nuclei, YAP would remain outside of the nucleus and the stem cells would become bone cells. Whereas, when the researchers compressed the MSCs, their nuclei would elongate, YAP would then enter the nuclei, and the stem cells would become fat cells.

Dr Ehrlicher and his team believe that this discovery could aid bone regeneration treatments in patients after traumatic incidents or those with osteoporosis. However, they also advise that it will likely be more than a decade before this new knowledge translates from the lab into the clinic.

The next steps will involve translating their research from 2D single cell layers to 3D cultures, which will help the researchers understand how stem cells will respond to the mechanical stimuli in the human body.