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Updated: Jun 6, 2025
Human Ex vivo Wound Model and Whole-Mount Staining Approach to Accurately Evaluate Skin Repair
Published on: February 17, 2021
Liver Fluke-Derived Molecules Accelerate Skin Repair Processes in a Mouse Model of Type 2 Diabetes Mellitus
Anna Kovner1, Yaroslav Kapushchak1, Oxana Zaparina1
1Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (ICG SB RAS), 10 Akad. Lavrentiev Ave., Novosibirsk 630090, Russia.
Abstract:
Chronic nonhealing wounds, such as diabetic ulcers, are among the most serious complications of diabetes mellitus. Consequently, the search for new therapeutic strategies remains highly relevant. Based on our previous data on acute wounds, bioactive molecules derived from the liver fluke Opisthorchis felineus hold promise as a novel approach to wound healing. The aim of this study was to investigate the wound-healing properties of excretory-secretory products (ESP) and inactivated eggs of O. felineus in a model of type 2 diabetes mellitus. Two-month-old mice of the BKS.Cg + Leprdb/+Leprdb/OlaHsd (db/db) strain were inflicted with superficial wounds of 5 mm in diameter. Mouse groups included several controls (methylcellulose as the vehicle and human recombinant PDGF as the positive control) and specific-treatment groups (ESP and inactivated O. felineus eggs). Histopathological, immunohistochemical, and RT-PCR studies using markers for M1/M2 polarization, angiogenesis, and extracellular matrix remodeling were carried out. Additionally, an image analysis of Masson's trichrome-stained skin sections was performed. The proliferation of HaCaT cells under ESP and egg treatment was also assessed. The present study reveals a significant increase in the percentage of wound healing in ESP- and egg-treated groups, which significantly exceeded the control values after 14 days. Wound treatment with either ESP or worm eggs resulted in (i) a reduction in inflammation with a canonical M1-to-M2 polarization shift, (ii) the modulation of the vascular response, and (iii) dermal extracellular matrix remodeling. All results are comparable to those of the positive control group treated with PDGF. This study also reveals that ESP, but not O. felineus eggs, stimulated keratinocyte proliferation in vitro. The results indicate the high wound-healing potential of liver fluke bioactive molecules and open prospects for further research on these new promising therapeutic approaches.
Insights
Bioactive molecules from the liver fluke Opisthorchis felineus, including excretory-secretory products (ESP) and eggs, significantly accelerate chronic wound healing in diabetic mice. These compounds reduce inflammation and promote tissue repair, offering a novel therapeutic approach.
Area of Science:
- Biochemistry
- Parasitology
- Dermatology
- Regenerative Medicine
Background:
- Chronic nonhealing wounds, like diabetic ulcers, represent a significant clinical challenge.
- Existing treatments are limited, necessitating novel therapeutic strategies.
- Bioactive molecules from Opisthorchis felineus have shown potential in acute wound healing.
Purpose of the Study:
- To investigate the wound-healing properties of Opisthorchis felineus excretory-secretory products (ESP) and inactivated eggs.
- To evaluate these properties in a type 2 diabetes mellitus mouse model.
- To assess the effects on inflammation, angiogenesis, and extracellular matrix remodeling.
Main Methods:
- Superficial wounds were inflicted on db/db mice (type 2 diabetes model).
- Mice were treated with O. felineus ESP, inactivated eggs, or controls (vehicle, PDGF).
- Histopathology, immunohistochemistry, RT-PCR, and cell proliferation assays were performed.
Main Results:
- ESP and egg treatments significantly increased wound healing percentage compared to controls after 14 days.
- Treatments reduced inflammation (M1-to-M2 polarization shift), modulated vascular response, and promoted extracellular matrix remodeling.
- ESP stimulated keratinocyte proliferation in vitro, while eggs did not.
Conclusions:
- Bioactive molecules from O. felineus demonstrate significant wound-healing potential in a diabetic model.
- These molecules modulate key processes involved in tissue repair, comparable to PDGF.
- O. felineus derivatives offer promising avenues for developing new therapies for chronic nonhealing wounds.
