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Cytotherapy2018; 20(8); 1061-1076; doi: 10.1016/j.jcyt.2018.06.005

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.

Abstract: Impaired cutaneous wound healing is common in humans, and treatments are often ineffective. Based on the significant emotional and economic burden of impaired wound healing, innovative therapies are needed. The potential of mesenchymal stromal cell (MSC)-secreted factors to treat cutaneous wounds is an active area of research that is in need of refinement before effective clinical trials can be initiated. The aims of the present study were to (i) study which MSC-secreted factors stimulate dermal fibroblast (DF) migration in vitro and (ii) evaluate the potential of these factors to promote wound healing in vivo. To this end, MSCs were isolated from the peripheral blood of healthy horses, a physiologically relevant large animal model appropriate for translational wound-healing studies. Conditioned medium (CM) from cultured equine MSCs was analyzed using liquid chromatography-mass spectrophotometry (LC-MS/MS) to identify secreted proteins of interest. Double-stranded RNA-mediated interference (RNAi) was used to silence the genes encoding selected proteins, and the effects of CM from these transfected MSCs on migration of cultured equine DF cells in vitro and full-thickness wounds in mice were evaluated. We found that MSC-derived plasminogen activator inhibitor-1 (PAI-1) and tenascin-C significantly increased DF migration in vitro and improved wound healing in vivo by decreasing time to wound closure. These results suggest that in a complex wound environment, MSC-secreted factors PAI-1 and tenascin-C contribute to the positive effect of therapeutically applied MSC CM on wound healing.
Copyright © 2018 Elsevier Ltd. All rights reserved.
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Publication Date: 2018-08-04 PubMed ID: 30087008DOI: 10.1016/j.jcyt.2018.06.005Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • N.I.H.
  • Extramural
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

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.

Cite This Article

APA
Harman RM, He MK, Zhang S, VAN DE Walle GR. (2018). 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. Cytotherapy, 20(8), 1061-1076. https://doi.org/10.1016/j.jcyt.2018.06.005

Publication

Cytotherapy
ISSN: 1477-2566
NlmUniqueID: 100895309
Country: England
Language: English
Volume: 20
Issue: 8
Pages: 1061-1076

Researcher Affiliations

Harman, Rebecca M
  • Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States.
He, Megan K
  • Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States.
Zhang, Sheng
  • Proteomic and Mass Spectrometry Facility, Cornell University, Ithaca, New York, United States.
VAN DE Walle, Gerlinde R
  • Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States. Electronic address: grv23@cornell.edu.

MeSH Terms

  • Animals
  • Cell Line
  • Cell Movement / drug effects
  • Coculture Techniques
  • Culture Media, Conditioned / pharmacology
  • Dermis / cytology
  • Dermis / drug effects
  • Extracellular Vesicles / metabolism
  • Extracellular Vesicles / physiology
  • Female
  • Fibroblasts / drug effects
  • Fibroblasts / physiology
  • Horses
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • NIH 3T3 Cells
  • Plasminogen Activator Inhibitor 1 / metabolism
  • Plasminogen Activator Inhibitor 1 / pharmacology
  • Tenascin / metabolism
  • Tenascin / pharmacology
  • Wound Healing / drug effects
  • Wound Healing / physiology

Grant Funding

  • S10 OD017992 / NIH HHS

Citations

This article has been cited 24 times.
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