Larger and faster organoid growth achieved using cell squeezing

Researchers at Massachusetts Institute of Technology and Boston Children’s Hospital (both MA, USA) have revealed that physically squeezing cells (also referred to as cell squeezing), in addition to crowding their contents, can trigger them to grow and divide faster than they normally would.

The team explained that while it sounds like cell squeezing could be counterintuitive, squeezing acts to wring water out of a cell. With less water, proteins and other cell components are packed closer together and this can trigger cell signaling and activate genes within a cell due to the close proximity.

Within their study, which has been published in Cell Stem Cell, the scientists focused on several proteins that are known to trigger Wnt/β-catenin signaling – a pathway that is involved in cell growth and maintenance of ‘stemness’.

“In general, this pathway is known to make a cell more like a stem cell. If you change this pathway’s activity, how cancer progresses and how embryos develop have been shown to be very different. So, we thought we could use this pathway to demonstrate how cell crowding is important,” explained study author, Ming Guo (Massachusetts Institute of Technology).

To determine whether cell squeezing affects the Wnt pathway and how quickly a cell grows, the investigators grew small organoids using clusters of cells that were collected from the intestines of mice.

The team grew intestinal organoids that measured approximately half a millimeter each in several Petri dishes. They then ‘squeezed’ the organoids by infusing the dishes with polymers. This resulted in an increase in osmotic pressure surrounding each organoid, which forced water out of their cells.

As a result of this, the team observed that specific proteins involved in the Wnt pathway were packed closer together and were more likely to cluster to turn on the pathway and its growth-regulating genes. Additionally, organoids that were ‘squeezed’ resulted in larger and faster growth, with more stem cells present on their surface compared with organoids that were not squeezed.

In future, the researchers hope to explore cell squeezing as a way to speed up the growth of artificial organs that researchers may use to test new and personalized drugs.

Link: https://www.regmednet.com/larger-and-faster-organoid-growth-achieved-using-cell-squeezing/