Abstract
Regeneration and wound healing are vital to tissue homeostasis and organism survival. One of the biggest challenges of today’s science and medicine is finding methods and factors to stimulate these processes in the human body. Effective solutions to promote regenerative responses will accelerate advances in tissue engineering, regenerative medicine, transplantology, and a number of other clinical specialties. In this study, we assessed the potential efficacy of a synthetic hexapeptide, RDKVYR, for the stimulation of tissue repair and wound healing. The hexapeptide is marketed under the name “Imunofan” (IM) as an immunostimulant. IM displayed stability in aqueous solutions, while in plasma it was rapidly bound by albumins. Structural analyses demonstrated the conformational flexibility of the peptide. Tests in human fibroblast and keratinocyte cell lines showed that IM exerted a statistically significant (p < 0.05) pro-proliferative activity (30–40% and 20–50% increase in proliferation of fibroblast and keratinocytes, respectively), revealed no cytotoxicity over a vast range of concentrations (p < 0.05), and had no allergic properties. IM was found to induce significant transcriptional responses, such as enhanced activity of genes involved in active DNA demethylation (p < 0.05) in fibroblasts and activation of genes involved in immune responses, migration, and chemotaxis in adipose-derived stem cells derived from surgery donors. Experiments in a model of ear pinna injury in mice indicated that IM moderately promoted tissue repair (8% in BALB/c and 36% in C57BL/6 in comparison to control).
Highlights
Wound healing complications after trauma, surgery, acute illness, or chronic disease conditions, and subsequent appearance of chronic wounds, affect millions of people worldwide each year
We examined the effect of IM on the secretion of specific growth factors and cytokines by fibroblasts, keratinocytes, and adipose-derived stem cells stem (ASCs)
The study presents a complex evaluation of the peptide RDKVYR (IM) as a potential wound healing agent
Summary
Wound healing complications after trauma, surgery, acute illness, or chronic disease conditions, and subsequent appearance of chronic wounds, affect millions of people worldwide each year. Delayed healing is often caused by dysregulation of the response to wounding resulting from inflammation, angiogenesis, matrix deposition, and/or cell recruitment. The inability to restore the function and architecture of injured tissues is typical of chronic skin wounds resulting from thermal, chemical, or radiation burns of a large area, as well as civilization diseases such as diabetes or atherosclerosis. The need for clinical strategies that might activate natural repair mechanisms leading to scarless wound healing and tissue repair is still growing [1]. One of the possible strategies is pharmacological stimulation of natural regenerative processes in the body. Peptides, which are biocompatible, biodegradable, bioactive, and relatively amenable to large-scale production, are currently gaining interest as potential agents in regenerative medicine. Among many biologically active molecules is the RDKVYR peptide, which is known as thymohexin and marketed as Imunofan (IM). IM is a hydrophilic hexapeptide which was designed based on the sequence at positions 32–37 of the thymopoietin hormone (RKDVYV)
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