Secreted factors from equine mesenchymal stromal cells diminish the effects of TGF-β1 on equine dermal fibroblasts and alter the phenotype of dermal fibroblasts isolated from cutaneous fibroproliferative wounds.

This study investigates the potential of substances released by equine mesenchymal stromal cells (MSCs) to minimize disorders of skin overgrowth in wound healing, seen in conditions like keloids in humans, and excessive tissue growth in horses. The research found that these substances can moderate the negative effects of a specific cytokine, TGF-β1, and even modify the behavior of fibroblast cells from wound sites with these overgrowth disorders, suggesting a future therapeutic avenue for these conditions.

Overview of the Research Issue

• Cutaneous Fibroproliferative Disorders (CFPDs) are conditions where skin wounds heal with an overgrowth of tissue, contributing to scarring. Prominent among these are keloids and hypertrophic scars in humans, and exuberant granulation tissue in horses. These CFPDs are the result of an imbalance in the wound healing process.
• Key among the factors causing this imbalance is a cytokine named Transforming Growth Factor Beta 1 (TGF-β1) which stimulates excessive growth of the skin’s connective tissue, distorting the normally ordered layering of these cells known as Dermal Fibroblasts (DF).

The Role of Mesenchymal Stromal Cells (MSCs)

• Mesenchymal Stromal Cells (MSCs) secrete a variety of bioactive substances (known collectively as the MSC secretome) that have been found to promote normal wound healing in humans and horses. The prospect of employing these substances to treat CFPDs, however, hasn’t been thoroughly investigated before.

Research Methodology and Results

• This study begins with a laboratory examination of the effects of the equine MSC secretome on equine DFs stimulated by TGF-β1. It was observed that the MSC secretome was able to combat the TGF-induced changes in the DF cells’ structure, growth rate, gene expression, and contraction ability.
• The team isolated primary DF cells from chronic horse wounds to test the effect of the MSC secretome on cells from an actual CFPD environment. The results did not demonstrate significant changes in cell growth or migration. However, it was seen to alter the expression of genes and proteins involved in rebuilding the extracellular matrix, while also affecting contraction.

Conclusion and Future Implications

• The findings of this study decidedly indicate the potential of the MSC secretome in controlling CFPD-related pathologies, justifying future investigations to evaluate its application as a possible therapeutic strategy.