БиоПро Выбор потребителя 2018 #02

Antibacterial properties of mesenchymal stem cells will help fight MRSA and other superbugs

A study by scientists from Cornell University, US, showed that the antimicrobial properties of some proteins produced by mesenchymal stem cells (MSCs) could be used to develop potential treatments for infected wounds.

According to new work by researchers at the Baker Institute for Animal Health, part of the College of Veterinary Medicine (CVM) at Cornell University, treating wounds with factors secreted by mesenchymal stem cells effectively reduces vitality methicillin-resistant Staphylococcus aureus (MRSA). Moreover, the researchers found that the secretion stimulated the surrounding skin cells to create a defense against bacterial infection.

“The results showed that secreted factors from equine mesenchymal stromal cells (MSCs), a type of stem cell, significantly decreased the viability of MRSA in our novel skin model”, – said the first author of the article, published in the journal Stem Cells Translational Medicine, Dr. Charlotte Marx, a researcher in the laboratory of Dr. Gerlinde R. Van de Walle, associate professor of microbiology and immunology at CVM.

“Moreover”, – Marx said, “we demonstrated that equine MSC secretions increase the antimicrobial activity of the skin cells by stimulating immune responses of the surrounding resident skin cells.”

In 2017, over 119,000 people in the United States were affected, and nearly 20,000 died from bloodstream infections caused by MRSA, according to the latest statistics from the Centers for Disease Control and Prevention. Methicillin-resistant Staphylococcus aureus has become a serious public health problem despite many people carrying this infection without serious consequences. Under certain circumstances, it can pose a threat, for example, to immunocompromised patients or infection of wounds. In addition, MRSA is resistant to many antibiotics – the only drugs currently available to treat bacterial infections.

New research could pave the way for a cure for MRSA infection. The key solution to this problem is mesenchymal stem cells, which can be isolated from bone marrow, fat, blood, and other tissues.

“Initially, the use of MSCs for tissue regeneration was advocated based on their ability to differentiate into various tissue types”, – Van de Walle said. “For this reason, it was anticipated that injected MSCs colonize the injury site, differentiate into the appropriate tissue type, and regenerate the damaged tissue.”

However, research shows that only a small fraction of the injected MSCs are actually incorporated into the damaged tissue, she said.

“For this reason, it is becoming generally accepted that the beneficial effects in tissue repair and regeneration are more likely indirect, depending on the effects of what these cells secrete”, – Van de Walle said. “Such cell-free therapies might prove safe and potentially more advantageous alternatives by overcoming the risks and obstacles associated with the use of the cells themselves.”

Several previous scientific reports have shown that mesenchymal stem cells reduce levels of inflammation. However, in a study conducted at Cornell, scientists went further by studying the effect of MSC secretion, also known as secretome, on the antimicrobial defense mechanisms of skin cells and testing its efficacy with biofilms on a physiologically relevant equine skin model.

According to Van de Walle, horses were used in the study because, like in humans, certain types of chronic wounds are often resistant to treatment and cause various complications, leading to high morbidity and mortality.

The team began testing by creating an equine skin biofilm model. Biofilms are populations of microorganisms that develop on surfaces. In this state, bacteria are well protected from antibiotics, even if they are not resistant. The skin samples from the skin of horses that had to be euthanized for reasons unrelated to the study were cultured over three days. During the culturing period, cell death and epidermal thickness remained stable.

The research team then created a model of an infected wound by making identical punctures in skin samples and inoculating them with either MRSA or its antibiotic-sensitive counterpart, methicillin-susceptible Staphylococcus aureus (MSSA). Further, the wounds were treated for 24 hours with either antibiotics or the usual medium (which served as a control in the experiment) or mesenchymal stem cells secretome. At the end of the treatment period, the researchers measured the bacterial load by assessing colony-forming units per gram of tissue.

“The findings contribute to understanding the MSC secretome’s antimicrobial properties and further support the value of MSC secretome-based treatments for infected wounds”, – Marx said.

“By identifying additional effective treatments”, – she said, “we can contribute to reducing the use of antibiotics in both veterinary and human medicine, which is important for the fight against antibiotic resistance.”