Stem cells differentiate in response to physical pressure

Squeezing human stem cells through confined spaces can generate bone-forming cells, according to new research.

Stem cells have the potential to transform into different cell types within the body, by becoming specialised, through a process called differentiation. To alter their cell fate, stem cells have been traditionally exposed to different chemical cues to stimulate their desired differentiation pathway. However, scientists from the National University of Singapore (NUS) have discovered that squeezing stem cells through narrow spaces can encourage stem cells to differentiate into bone-forming cells.

'To test how physical forces influence stem cell fate, we developed a specialised microchannel system that mimics the narrow tissue spaces cells navigate in the body,' said Dr Andrew Holle, from the NUS Department of Biomedical Engineering and corresponding author of the study published in Advanced Science. 'What our study shows is that physical confinement alone – squeezing through tight spaces – can also be a powerful trigger for differentiation.'

Dr Holle and his colleagues used bone marrow-derived mesenchymal stem cells (MSCs), which can form blood, fat and bone cells. Forcing these human MSCs through extremely narrow channels – three micrometers wide – increased the speed at which the MSCs moved through the channels and induced long-lasting structural changes within the MSCs, even after they exited the channels. This implied that the MSCs remembered the physical stress of their confinement, influencing how they behaved in the future.

The physical pressure inflicted on the MSCs increased the activity of an essential gene for bone formation known as RUNX2. Therefore, physical confinement can act as a key mechanical prompt for promoting the early differentiation of MSCs into bone-forming cells, without the need for chemical cues, providing a simpler way to steer cell fates.

This research may have broader implications that the team in Singapore want to investigate in the future. Mechanically-stressed MSCs with advanced migration could potentially aid in healing at injury sites or movement through dense tumour tissue – a limitation experienced in previous cell therapies. Moreover, the research team believes that this technique could be applied to induced pluripotent stem cells (iPSCs) – a more versatile type of stem cell which can differentiate into nearly all cell types – to determine whether physical pressure can influence other pathways of cell fate.

'We suspect that confinement plays a role even in embryonic development,' said Dr Holle. 'Cells migrating through crowded environments early in life are exposed to mechanical stress that could shape their fate. We think this idea has potential far beyond just MSCs.'