A new study finds that regardless of environment, adding or removing water from a stem cell could determine if it becomes a fat cell or a bone cell. The work was published earlier this week in Proceedings of the National Academy of Sciences.
Changes in cell volume are a result of variations in the amount of protein, DNA, and other materials within the cell, though they mostly remain constant. However, cells can experience rapid extreme cell volume changes in as little as 20 minutes.
When the volume of cells was increased by 20%, the researchers found that the cells experienced several internal changes, including in gene expression and stiffness. Knowing the role cell stiffness plays in the development of stem cells, the researchers began to wonder if cell volume could affect their fate as well.
To test their question, the researchers placed stem cells at their normal volume in a hardened hydrogel substrate to simulate the rigidness of bone cells. They also placed stem cells in a softened hydrogel substrate. They found that the stem cells in the both the hardened hydrogel substrate and softened hydrogel substrate became pre-bone cells. However, there were less pre-bone cells in the softened hydrogel substrate than the hardened hydrogel substrate.
When the researchers decreased the cell volume by 20% from the stem cells in the softened hydrogel substrate, they noticed that there was an increase in pre-bone cells.
Next, the researchers conducted a similar experiment using glass. They placed the stem cells on glass to simulate a stiff environment and found that few of the cells developed into pre-fat cells. It was not until the volume of the stem cells was increased by 20% that a spike in the formation of fat cells was found.
"The surprising thing about these experiments is the observation that volume seems to be related to so much about the cell. It seems to dictate the cell stiffness as well as the cell fate. These observations may also have implications in external means of monitoring cell fate, which may be important for future biotech applications," explains David Weitz, Ph.D., Mallinckrodt Professor of Physics and of Applied Physics in the John A. Paulson School of Engineering and Applied Sciences at Harvard University.
The researchers believe that learning what causes differentiation among these cells will help scientists generate methods that influence their behavior and, ultimately, develop new therapies.
Image: Top images (A): The development of stem cells on hydrogel, a soft substrate, to pre-bone cells after the removal of water. Bottom images (B): The development of stem cells on glass, a hard substrate, to pre-fat cells after the addition of water.