Plasminogen activator inhibitor-1 and tenascin-C secreted by equine mesenchymal stromal cells stimulate dermal fibroblast migration in vitro and contribute to wound healing in vivo.

The research study focuses on exploring the influence of factors secreted by mesenchymal stromal cells (MSCs) on stimulating skin cell migration for effective wound healing, in vitro and in vivo. The study identified that plasminogen activator inhibitor-1 and tenascin-C notably enhance skin cell migration and accelerate wound healing.

Study of MSC-Secreted Factors

The researchers aimed to:

• Study which factors released by mesenchymal stromal cells (MSCs) stimulate skin cell (dermal fibroblast, DF) migration in a controlled laboratory setting (in vitro).
• Assess these factors’ ability to promote wound healing in a living body (in vivo).

For a physiologically relevant model for wound healing studies, they used MSCs isolated from the peripheral blood of healthy horses. They used conditioned medium (CM) – culture medium that previously hosted cells and contains their secretions – from equine MSCs for analysis.

Identification of Secreted Proteins

• The researchers utilized a procedure known as liquid chromatography-mass spectrophotometry (LC-MS/MS) to identify proteins secreted by the MSCs of interest. LC-MS/MS is an effective tool for separating, identifying and quantifying individual components in a mix.

Silencing Selected Proteins

• They employed RNA interference (RNAi), a biological process where RNA molecules impede gene expression, to mute the genes encoding selected proteins.
• The study then examined the effects of CM from these gene-silenced MSCs on the migration of cultured equine DF cells in vitro and on full-thickness wounds in mice in vivo.

Results and Conclusion

• The researchers discovered that two factors, plasminogen activator inhibitor-1 and tenascin-C, originating from MSC exhibited a consistent increase in DF migration in vitro.
• A significant improvement in wound healing in vivo was also observed, characterized by a decrease in time required for wound closure.

The results indicate that in a complex wound environment, MSC-secreted factors plasminogen activator inhibitor-1 and tenascin-C could contribute to the positive effect of therapeutically applied MSC CM on wound healing. This potentially opens new avenues for effective wound healing treatments.