Mesenchymal stromal cells from horses show potential for healing skin wounds

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Equine mesenchymal stromal cells have been shown to have antibacterial properties, raising the possibility they could aid in healing troublesome skin wounds in humans and horses.

Mesenchymal stem cells, or MSCs, are multipotent connective-tissue cells that can differentiate into a variety of cell types, including bone cartilage, muscle and fat.

Chronic skin wounds in humans are common and their treatment is often complicated by pathogenic bacteria. Therefore, safe and innovative treatments to reduce the bacterial load in such wounds are needed.

MSCs have been reported to provide local hormonal signals that promote healing in skin wounds. However, the effects of equine MSCs on the growth of bacteria commonly found in skin wounds has not, until now, been explored.

Researchers from the College of Veterinary Medicine at New York’s Cornell University have been the first to show that equine MSCs possess antimicrobial properties which stymied the growth of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus).

The MSCs did so in part by secreting antimicrobial peptides and depolarizing the bacterial cell membranes.

Rebecca Harman, Gerlinde Van de Walle, Steven Yang, and Megan He, writing in the journal Stem Cell Research & Therapy, said they focused on the antibacterial properties of MSCs from horses, as this animal model offered a readily translatable model for therapies in humans.

The study team described the laboratory experiment they set up, in which MSCs were isolated from the blood of healthy horses. The bacteria were cultured in the presence of MSCs and an MSC conditioned medium – a processed fluid containing all factors secreted by the cells.

They found that both the MSCs and the MSC conditioning medium inhibited the growth of both bacteria, and that the conditioning medium depolarized the cell membranes of these bacteria.

The conditioning medium was found to contain four antimicrobial peptides, cystatin C, elafin, lipocalin 2, and cathelicidin. These appeared to be at least partially responsible for the antibacterial action.

They also looked for the presence of beta defensin 2 in equine MSCs since it has been found to be secreted by human umbilical cord-derived MSCs. It belongs to a widespread family of antimicrobial peptides found in most mammals, including horses. To the surprise of the research team, they could not detect beta defensin 2 in equine MSCs.

“Our results,” they concluded, “demonstrate that equine MSCs inhibit bacterial growth and secrete factors that compromise the membrane integrity of bacteria commonly found in skin wounds.”

There appeared to be a difference in the underlying mechanisms targeting each species, with different secreted factors appearing to target different bacteria.

It will be interesting, they said, to study the effects of the MSC conditioning medium on additional bacterial species commonly found in equine skin wounds. The findings will likely be relevant to human as well as veterinary medicine, they said.

“Since we found that equine MSCs secrete a variety of antimicrobial peptides that appear effective against both gram-positive [S. Aureus] and gram-negative [E.Coli] bacteria, these cells may serve as a broad-spectrum treatment to control bacterial growth and kill bacteria, without leading to resistance.”

The study team said they now intended to evaluate the effectiveness of equine MSCs in healing both acute and chronic wounds.

Antimicrobial peptides secreted by equine mesenchymal stromal cells inhibit the growth of bacteria commonly found in skin wounds
Rebecca M. Harman, Steven Yang, Megan K. He and Gerlinde R. Van de Walle
Stem Cell Research & Therapy 2017 8:157 DOI: 10.1186/s13287-017-0610-6

The study, published under a Creative Commons License, can be read here

 

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