Sensational discovery was made by scientists from the University at Buffalo, USA. In a paper, published in the Proceedings of the National Academy of Sciences of the United States of America (PNAS), researchers argue that the fate of mesenchymal stem cells (MSCs) can be controlled by dehydrating them or adding excess water to them.
The study showed that a change in the volume of a cell changes its internal dynamics, as well as the rigidity of its surrounding membrane. Removal of water from mesenchymal stem cells condenses them, making the structure more rigid. Such MSCs become stiff pre-bone cells. Addition of water leads to swelling of MSC, which leads to the formation of soft pre-fat cells.
Scientists have long understood that the stiffness of external membranes of cells from their environment influences the further formation of stem cells.
Initially, researchers from Buffalo intended to study the effect of volume on the characteristics and functions of cells. Volume – the value is strictly regulated and often varies throughout the life of the cell, increasing during growth and decreasing during division.
Such volume changes are the result of changes in the number of proteins, DNA and other constituent cells, although they remain largely constant. However, cells can quickly change size and density by absorbing or releasing water, expanding or contracting in just 20 minutes.
Scientists have found that a decrease in volume by 20% affects some intracellular processes, including gene expression and stiffness. Knowing that stiffness plays an important role in the development of stem cells, the researchers wondered if the volume could also affect their fate.
To clarify this issue, the researchers placed mesenchymal stem cells in a dense hydrogel substrate to simulate the rigidity of bone cells. After about 7 days, most of the MSC was differentiated into pre-bone cells.
The experiment was repeated with a soft hydrogel substrate. In this case, there was a decrease in the number of cells that turned into pre-bone. However, after the removal of water from the cells to reduce their volume by 20%, the number of MSCs that have become pre-bone cells enlarged, despite the fact that they were in a softer environment.
A analogous experiment was carried out using glass. The researchers placed stem cells on it to mimic a tougher environment, and found that some of the cells turned into pre-fat cells. When the volume of MSC was increased by 20% due to the addition of water, a surge of formation of fat cells was observed.
“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,” – says David Weitz, PhD, co-author of study. “These observations may also have implications in external means of monitoring cell fate, which may be important for future biotech applications.”
Further investigations are needed to study the effect of various volume changes in order to determine whether the dominating factor in the fate of stem cells is the volume or, still, external signals.
Stem cells are currently the highest priority in regenerative medicine, providing researchers and clinicians with the opportunity to repair or replace damaged tissues and organs.
Due to the ability to differentiate into specialized cells of any type of tissue – from myocytes to blood or brain cells – stem cells have the potential to treat various diseases and pathologies. The widely available method of therapy using MSCs obtained from adipose tissue of the patient is widely used all over the world.
Stem cells also contribute to the development of new drugs and the understanding of the occurrence of congenital defects.
Studying the factors that influence the differentiation of stem cells will help scientists create methods that affect their behavior, which, ultimately, will help in creating new therapeutic approaches.
In addition to physical signals, such as stiffness or cell volume, a number of biological factors, pharmaceutical preparations or biophysical agents, such as light, radio frequencies and ultrasound, can also influence the differentiation of MSCs.