Extracellular vesicles secreted by equine adipose mesenchymal stem cells preconditioned with transforming growth factor β-1 are enriched in anti-fibrotic miRNAs and inhibit the expression of fibrotic genes in an in vitro system of endometrial stromal cells fibrosis.
Abstract: Mare endometrosis is a major reproductive problem associated with low fertility and is characterized by persistent inflammation, TGFβ-1 signaling, and consequently, extracellular matrix deposition, which compromises endometrial glands. Mesenchymal stem cell-based products (MSCs), such as extracellular vesicles (EVs), have gained attention due to the regulatory effects exerted by their miRNA cargo. Here, we evaluated the impact of preconditioning equine adipose mesenchymal stem cells with TGFβ-1 for short or long periods on the anti-fibrotic properties of secreted extracellular vesicles. MSCs were isolated from six healthy horses and exposed to TGFβ-1 for 4, 24, and 0 h. The expression of anti-fibrotic and pro-fibrotic miRNAs and mRNAs in treated cells and miRNAs in the cargo of secreted extracellular vesicles was measured. The resulting EVs were added for 48 h to endometrial stromal cells previously induced to a fibrotic status. The expression of anti-fibrotic and pro-fibrotic genes and miRNAs was evaluated in said cells using qPCR and next-generation sequencing. Preconditioning MSCs with TGFβ-1 for 4 h enriched the anti-fibrotic miRNAs (mir29c, mir145, and mir200) in cells and EVs. Conversely, preconditioning the cells for 24 h leads to a pro-fibrotic phenotype overexpressing mir192 and mir433. This finding might have implications for developing an EV-based protocol to treat endometrial fibrosis in mares.
Publication Date: 2024-07-31 PubMed ID: 39086189PubMed Central: PMC11295685DOI: 10.1080/01652176.2024.2384906Google Scholar: Lookup
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- Journal Article
Summary
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The research suggests that extracellular vesicles (EVs) from horse fat-derived stem cells, primed with a certain growth factor, are enriched with molecules that prevent tissue scarring and can inhibit genes associated with fibrosis. This could be potentially useful in treating endometrial fibrosis in mares.
Objective and Background
- The study seeks to evaluate the impact of priming or preconditioning equine adipose mesenchymal stem cells with transforming growth factor TGFβ-1 on the anti-fibrotic properties of the extracellular vesicles (EVs) they produce.
- The research is significant due to the issue of endometrosis in mares, a reproductive problem related to low fertility. The disease is characterized by persistent inflammation and the excessive deposition of extracellular matrix which damage the endometrial glands.
- Study’s interest is focused on mesenchymal stem cell-based products (MSCs), in particular, extracellular vesicles (EVs), due to their regulatory effects carried out by miRNA or microRNA cargo they contain.
Methodology
- Stem cells were taken from six healthy horses and exposed to the transforming growth factor TGFβ-1 for different periods – 0 hours, 4 hours, and 24 hours.
- The researchers then studied the presence and quantities of specific anti-fibrotic and pro-fibrotic miRNAs and mRNAs in treated cells and miRNAs in the cargo of secreted extracellular vesicles.
- These EVs were then introduced to endometrial stromal cells that had previously been induced to a fibrotic status, and were incubated for 48 hours.
- The expression of anti-fibrotic and pro-fibrotic genes and miRNAs was then evaluated in these cells, using qPCR and next-generation sequencing techniques.
Findings and Implications
- The investigators found that preconditioning the MSCs with TGFβ-1 for 4 hours enriched the anti-fibrotic miRNAs (mir29c, mir145, and mir200) in cells and EVs.
- However, preconditioning the cells for 24 hours led to a pro-fibrotic phenotype overexpressing mir192 and mir433.
- These findings can have significant implications in the development of an EV-based protocol to treat endometrial fibrosis in mares, a common disease that affects equine fertility.
Cite This Article
APA
Wong YS, Mançanares AC, Navarrete F, Poblete P, Mendez-Pérez L, Cabezas J, Riadi G, Rodríguez-Alvarez L, Castro FO.
(2024).
Extracellular vesicles secreted by equine adipose mesenchymal stem cells preconditioned with transforming growth factor β-1 are enriched in anti-fibrotic miRNAs and inhibit the expression of fibrotic genes in an in vitro system of endometrial stromal cells fibrosis.
Vet Q, 44(1), 1-11.
https://doi.org/10.1080/01652176.2024.2384906 Publication
Researcher Affiliations
- Department of Animal Science, Faculty of Veterinary Sciences, Universidad de Concepción, Chillán, Chile.
- Department of Animal Science, Faculty of Veterinary Sciences, Universidad de Concepción, Chillán, Chile.
- Department of Animal Science, Faculty of Veterinary Sciences, Universidad de Concepción, Chillán, Chile.
- Ph.D. Program on Veterinary Sciences, Faculty of Veterinary Sciences, Universidad de Concepción, Chillán, Chile.
- Ph.D. Program on Veterinary Sciences, Faculty of Veterinary Sciences, Universidad de Concepción, Chillán, Chile.
- Department of Animal Science, Faculty of Veterinary Sciences, Universidad de Concepción, Chillán, Chile.
- Center for Bioinformatics Simulation and Modeling (CBSM), Universidad de Talca, Talca, Chile.
- Department of Animal Science, Faculty of Veterinary Sciences, Universidad de Concepción, Chillán, Chile.
- Department of Animal Science, Faculty of Veterinary Sciences, Universidad de Concepción, Chillán, Chile.
MeSH Terms
- Animals
- Horses
- Female
- Mesenchymal Stem Cells / metabolism
- MicroRNAs / genetics
- MicroRNAs / metabolism
- Extracellular Vesicles / metabolism
- Fibrosis
- Transforming Growth Factor beta1 / metabolism
- Transforming Growth Factor beta1 / genetics
- Endometrium / metabolism
- Endometrium / cytology
- Adipose Tissue / cytology
- Adipose Tissue / metabolism
- Stromal Cells / metabolism
- Stromal Cells / drug effects
- Horse Diseases
- Gene Expression Regulation / drug effects
- Endometriosis / veterinary
- Endometriosis / metabolism
- Endometriosis / genetics
Conflict of Interest Statement
No potential conflict of interest was reported by the author(s)
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