The therapeutic potential of mesenchymal stem cell vesicles could be increased tenfold

In a new study, scientists at the University of Illinois Chicago (UIC) have maximized the production of extracellular vesicles by simply changing the way donor mesenchymal stem cells (MSC) are cultured. This method opens up new possibilities for research in cell therapy using transplantation of stem cells or immune cells obtained from patients or donors.

The discovery will help patients improve their condition at minimal cost, and doctors will carry out treatment with maximum efficiency. For example, treatment with extracellular vesicles of MSCs has shown promising results in lung injuries caused by acute respiratory distress syndrome (ARDS). However, this method is expensive and limited by the number of donor cells required to achieve a therapeutic effect.

Researchers led by Jae-Won Shin studied the work mechanisms of extracellular vesicles of MSCs. Their experiments found that altering the components used to culture donor cells could significantly affect the therapeutic potential of extracellular vesicles.

“We were very surprised that a simple environmental change could have such a significant impact”, – said Shin, UIC assistant professor in the department of pharmacology and regenerative medicine and the department of biomedical engineering. “This tells us that cells interact differently in different tissues, and this impacts how they secrete extracellular vesicles and influence other cells around them.”

The researchers found that a critical factor in this process was using a soft hydrogel substrate that mimics tissue elasticity in vivo. The researchers compared extracellular vesicles produced by mesenchymal stem cells on a traditionally used rigid plastic substrate with MSC vesicles grown in softer material. The results showed that the secretion of vesicles per cell was about ten times higher in the latter case.

“In the stiff substrates, cytoskeletal structures in cells are dense and less flexible. This makes it difficult for extracellular vesicles to exit the cells. But in the soft substrate, these structures are less dense, more bendable, and more spread out, making the environment more conducive to the secretion of the particles by cells,” – said Stephen Lenzini, the first author of an article published in ACS Nano.

“That why fewer donor cells are needed to produce the same number of particles”, – Shin added.

The researchers also compared the therapeutic potential of vesicles secreted by MSCs when cultured using different materials. They noted that extracellular vesicles derived from cells grown in a softer substrate were much more efficient when used in regenerative processes than the same number of extracellular vesicles derived from MSCs cultured on a traditional rigid substrate.

“Understanding this opens the door for many new avenues of investigation for lab and clinical trials of treatments that use donor extracellular vesicles to repair damaged tissues, like which occurs in the lungs of some COVID-19 patients who face complications like ARDS”, – Shin said.