Mesenchymal Stromal Cells Help to Prevent MRSA Infection

Mesenchymal Stromal Cells Help to Prevent MRSA Infection

The secretions of a type of stem cell called mesenchymal stromal cells (MSCs) have been shown to reduce the viability of methicillin-resistant Staphylococcus aureus (MRSA) bacteria and could potentially be used to prevent and treat infections in hospitals.

Staphylococcus aureus is an invasive bacterium that has developed resistance to many widely used antibiotics. The ‘superbug’ known as MRSA is spread in the community through contact with items carrying the bacteria. The bacteria often enter the body through a cut in the skin, and while most infections are minor, the bacteria can be a serious problem in hospitals where they can enter the bloodstream through wounds. The resistance to most commonly used antibiotics can make infections difficult to treat, and infections can cause serious complications, especially in immunocompromised patients and infected wounds.

In the United States, 119,000 people had bloodstream infections involving MRSA in 2017, and almost 20,000 people died from their infections, according to data from the U.S Centers for Disease Control and Prevention. (CDC).

The natural solution to bacterial infections is antibiotics, but the broad resistance means new classes of antibiotics would be required. There may however be an alternative non-antibiotic treatment that could be administered in hospitals to prevent serious infections. A team of researchers at the Baker Institute for Animal Health at the Cornell University College of Veterinary Medicine, in Ithaca, NY have shown treating wounds with a secretion of MSCs stimulated the cells in the wound and provided protection against infection. MSCs can be easily isolated from fat, blood, bone marrow, and other tissues.

The use of MSCs was investigated to accelerate wound healing, as MSCs have the ability to differentiate into other cell types. The researchers found, however, that when introduced, most of the stem cells did not differentiate into the appropriate cells of the tissue where they were introduced to regenerate damaged tissue. Instead, the beneficial effects of using these cells appeared to be paracrine effects from the molecules secreted by the cells.

“This intriguing finding opens up novel therapeutic perspectives based on the development of cell-free regenerative therapies using the secretome of MSC that includes both soluble factors and factors released in extracellular vesicles,” said Gerlinde R. Van de Walle, DVM, Ph.D., associate professor of microbiology and immunology at Cornell and corresponding author of the study. “Such cell-free therapies might prove safe and potentially more advantageous alternatives by overcoming the risks and obstacles associated with the allogeneic use of the cells themselves.”

Then study was conducted as a follow to various studies that have shown that MSCs can have a positive effect by reducing inflammation, as no studies had been conducted to identify whether the molecules secreted by the MSCs had a positive effect on the body’s anti-microbial defenses. The effects of the cells were studied on horses, which also tend to suffer complications from infection with antibiotic-resistant bacteria.

The researchers established an equine skin biofilm model and cultured the skin samples for 3 days from freshly harvested equine skin. There was no significant increase in cell death or a decrease in epidermal thickness during the culturing period. The researchers then created an infected wound model by inoculating them with MRSA or methicillin-sensitive S. aureus (MSSA), and then measured bacterial load by measuring colony-forming units (CFU) per gram of tissue.

“The results showed that secreted factors from the MSCs significantly decreased the viability of MRSA in our novel skin model,” said study first author, Charlotte Marx, DVM, Ph.D., “Moreover, we demonstrated that equine MSC secretions increase the antimicrobial activity of the skin cells by stimulating immune responses of the surrounding resident skin cells.”

The study supports the use of proteins secreted by MSCs for use in both veterinary and human therapy for infected wounds, especially in cases of infection involving antibiotic-resistant bacteria.

You can read more about the study in the paper – Mesenchymal stromal cell‐secreted CCL2 promotes antibacterial defense mechanisms through increased antimicrobial peptide expression in keratinocytes – which was recently published in STEM CELLS Translational Medicine. DOI: 10.1002/sctm.21-0058