Researchers at the National University of Singapore (NUS) have discovered that human stem cells can be prompted to start becoming bone cells simply by squeezing through tight spaces. This innovative approach, which introduces a mechanical method to guide cell behavior, could revolutionize the field of regenerative medicine by offering a simpler, safer alternative to chemical and genetic interventions.
In an innovative breakthrough that could transform the field of regenerative medicine, researchers at the National University of Singapore (NUS) have discovered that human stem cells can be coaxed into becoming bone cells simply by moving through tight spaces.
Andrew Holle, an assistant professor of biomedical engineering in the College of Design and Engineering at NUS and the Mechanobiology Institute (MBI) at NUS, and his team made the striking finding that the physical act of squeezing through narrow channels can influence stem cell development.
This discovery introduces a new dimension to the ways researchers can guide cell behavior — beyond traditional chemical methods.
“Most people think of stem cell fate as being determined by chemical signals,” Holle said in a news release. “What our study shows is that physical confinement alone — squeezing through tight spaces—can also be a powerful trigger for differentiation.”
Holle’s lab developed a microchannel system designed to mimic the narrow spaces cells encounter within the body. This system allowed the team to observe how mesenchymal stem cells (MSCs) reacted to physical constraints.
These adult stem cells, which can develop into bone, cartilage and fat cells, showed significant changes when subjected to the smallest channels, just three micrometers wide.
The researchers found that the pressure from navigating these tight corridors activated a gene known as RUNX2, critical for bone formation. Remarkably, even after passing through the channels, the cells retained this activated state, suggesting they had a form of mechanical “memory.”
“This method requires no chemicals or genetic modification — just a maze for the cells to crawl through,” Holle added. “In theory, you could scale it up to collect millions of preconditioned cells for therapeutic use.”
These findings, published in the journal Advanced Science, could lead to significant advancements in how biomaterials and scaffolds for bone repair are designed.
By creating physical environments that naturally encourage the desired cell development, the approach promises a simpler, cost-effective and safer alternative to chemical and genetic interventions.
The potential applications are vast.
Holle and his team are keen to explore whether mechanically preconditioned cells can enhance healing when applied to injury sites.
Additionally, they see potential in improving cancer therapies. MSCs naturally migrate toward tumors, and the researchers are curious whether preconditioned cells might navigate dense tumor tissues more effectively — a major challenge in current cell therapies.
Looking ahead, the team is also interested in applying this technique to more versatile stem cells, such as induced pluripotent stem cells (iPSCs), which can develop into nearly any tissue type.
Holle suggests that mechanical stress might play a fundamental role even during embryonic development.
“We suspect that confinement plays a role even in embryonic development,” added 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.”
This research not only holds promise for enhancing bone repair but also sparks new possibilities for the broader field of regenerative medicine, potentially paving the way for groundbreaking therapies in the future.
Source: National University of Singapore