Organoids under pressure
How to make mini organs grow faster? Compress them
Tatiana Matveeva, "Scientific Russia"
This method is proposed by researchers from the Massachusetts Institute of Technology (MIT) and Boston Children's Hospital (USA). In an article published in the journal Cell Stem Cell (Chen et al., Volumetric Compression Induces Intracellular Crowding to Control Intestinal Organoid Growth via Wnt/β-Catenin Signaling), scientists have shown that physical compression of cells and accumulation of their contents can lead to cells growing and dividing faster than usual. This can significantly change the state of health and cell development, the MIT press service reports.
The cell division marker Ki67 shows that the number of dividing cells in organoids during three passages increases with compression (in the lower row). Image: Yiwei Li.
At first glance, it may seem counterintuitive that by squeezing something, we can make it grow. But the authors of the work have an explanation. By squeezing the cell, they remove water from the cell. With less water, proteins and other components of the cell are collected more compactly. And when certain proteins are in close proximity, they can trigger the transmission of signals in the cell and activate genes inside it.
In their new study, the scientists found that the compression of intestinal cells triggers the clustering of proteins along a specific signaling pathway that can help cells maintain the state of stem cells – cells that do not yet have a specific "profession", functions that can quickly grow and divide into more specialized cells.
If the cells can simply be compressed to provide this condition, then they can be directed to the rapid creation of miniature organs, such as an artificial intestine or colon. These mini-organs can then be used as models for studying organ function and testing drug candidates for various diseases, as well as as transplants for regenerative medicine.
Pack the contents of the cage
To study how compression affects cells, the researchers mixed different cell types in solutions that solidified as rubber plates of hydrogel. To compress the cells, the scientists placed a weight in the form of coins with a face value of 25 or 10 cents on the surface of the hydrogel.
"We wanted to achieve a significant change in the size of the cell, and these two loads can compress the cell by about 10-30 percent of their total volume," the authors explain.
The team used a confocal microscope to measure in 3D how the shapes of individual cells change when compressed. As they expected, the cells shrank from the pressure. But did the compression affect the contents of the cell? To answer this question, the researchers first looked at whether the amount of water in the cell had changed. They concluded that if squeezing squeezes water out of the cell, the cells should be less hydrated and become stiffer as a result.
They measured the stiffness of the cells twice: before they put the load, and after. Using optical tweezers, the scientists found that indeed the cells became rigid under pressure. They also saw that there was less movement inside the squeezed cells, suggesting that their contents were packed more tightly than usual.
The authors then looked at whether there were changes in the interactions between certain proteins in the cells in response to cell compression. They focused on several proteins that trigger Wnt/β-catenin signaling. This signaling pathway is involved in cell growth and maintains their "stem state". It also plays a role in the "renewal" of the intestinal mucosa.
"If you change the activity of this pathway, then how cancer progresses and how embryos develop will be very different. So we thought we could use this pathway to demonstrate the importance of cell aggregation," the researchers note.
The "updating" path
To see if cell compression affects the Wnt pathway and how fast the cells grow, the researchers grew small intestinal organoids (from mouse gut cells), each about half a millimeter in size, in several Petri dishes, and then "compressed" the organoids by impregnating the cups with polymers. This influx of polymers increased the osmotic pressure surrounding each organoid and displaced water from their cells. The team noticed that as a result, specific proteins involved in the activation of the Wnt pathway gathered closer together, probably in order to turn on this pathway and its growth-regulating genes.
The result: those organoids that were compressed actually grew bigger and faster. They had more stem cells on the surface than those organoids that did not compress. Scientists have also noticed that the behavior of a cell can change depending on the amount of water it contains.
In the future, the authors plan to study cell compression as a way to accelerate the growth of artificial organs that scientists can use to test new, personalized medicines.
Portal "Eternal youth" http://vechnayamolodost.ru